Engineering Plant Secondary Metabolism in …...108 alkaloids, giving rise to more than 3,000 structures. The tryptophan precursor anthranilate 109 also serves as a precursor to several

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Engineering Plant Secondary Metabolism in Microbial Systems 2

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Michael E. Pyne*, Lauren Narcross

*, Vincent J.J. Martin

*,1 4

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*Department of Biology, Centre of Applied Synthetic Biology, Centre for Structural and 7

Functional Genomics, Concordia University, Montréal, Québec, Canada 8

1 Corresponding author: E-mail address: [email protected] 9

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Short title: Producing plant secondary metabolites in microbes 11

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One-sentence summary: An overview of common challenges and 13

strategies underlying efforts to reconstruct plant isoprenoid, alkaloid, 14

phenylpropanoid, and polyketide biosynthetic pathways in microbial 15

systems. 16

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Author Contributions: M.E.P. and L.N. prepared the manuscript. 18

V.J.J.M supervised and edited the manuscript. All authors participated 19

in discussion and revision of the manuscript. 20

Plant Physiology Preview. Published on January 14, 2019, as DOI:10.1104/pp.18.01291

Copyright 2019 by the American Society of Plant Biologists

www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from Copyright © 2019 American Society of Plant Biologists. All rights reserved.

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Introduction 21

Secondary metabolites are broadly defined as natural products synthesized by an 22

organism that are not essential to support growth and life. The plant kingdom 23

manufactures over 200,000 distinct chemical compounds, most of which arise from 24

specialized metabolism. While these compounds play important roles in interspecies 25

competition and defense, many plant natural products have been exploited for use as 26

medicines, fragrances, flavors, nutrients, repellants, and colorants. 27

Despite this vast chemical diversity, many secondary metabolites are present at 28

very low concentrations in planta, eliminating crop-based manufacturing as a means of 29

attaining these important products. The structural and stereochemical complexity of 30

specialized metabolites hinders most attempts to access these compounds using chemical 31

synthesis. Although native plants can be engineered to accumulate target pathway 32

metabolites (Zhou et al., 2009; Glenn et al., 2013; Lange and Ahkami, 2013; Wilson and 33

Roberts, 2014; Tatsis and O’Connor, 2016), metabolic engineering is technically more 34

challenging in plants than in microbes. 35

Advancements in synthetic biology have stimulated the synthesis of valuable 36

natural products in tractable laboratory microbes by interfacing plant secondary pathways 37

with core host metabolism. Microbial synthesis overcomes many of the obstacles 38

hindering traditional chemical synthesis and plant metabolic engineering, thus providing 39

an alternative avenue for exploring plant specialized pathways. 40

This Update provides a brief overview of engineering plant secondary metabolism 41

in microbial systems. We briefly outline biosynthetic pathways mediating formation of 42

the major classes of natural products with an emphasis on high-value terpenoids, 43



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alkaloids, phenylpropanoids, and polyketides. We also highlight common themes, 44

strategies, and challenges underlying efforts to reconstruct and engineer these pathways 45

in microbial hosts. We focus chiefly on de novo biosynthetic approaches in which plant 46

specialized metabolites are synthesized directly from sugar feedstocks rather than 47

supplemented precursors or intermediates. Readers are directed to a selection of 48

pioneering supplementation studies within the context of microbially-sourced plant 49

natural products (Becker et al., 2003; Kaneko et al., 2003; Yan et al., 2005; Watts et al., 50

2006; Leonard et al., 2007; Hawkins and Smolke, 2008; Leonard et al., 2008; Fossati et 51

al., 2014; Fossati et al., 2015). 52

53

OVERVIEW OF KEY PLANT SECONDARY METABOLIC PATHWAYS 54

Terpenoids 55

Terpenoids (also called isoprenoids) are the largest class of plant secondary metabolites, 56

comprising more than 50,000 natural products (Connolly and Hill, 1991). Whereas the 57

terpene classification refers strictly to hydrocarbons, terpenoids possess a range of 58

chemical functionalities. The central precursors geranyl pyrophosphate (GPP; C10), 59

farnesyl pyrophosphate (FPP; C15), and geranylgeranylpyrophosphate (GGPP; C20) form 60

the structural basis of most higher-order terpenoids (Figure 1). Plant terpene synthases 61

convert these pyrophosphate intermediates to terpenes, which are then functionalized in 62

downstream reactions. 63

GPP forms the backbone of most monoterpenoids (C10), including linear (geraniol 64

and linalool) and cyclic (camphor and eucalyptol) terpenoids, as well as monoterpenes 65

(limonene and pinene). Geraniol can be modified to the pest repellant citronellol, while 66



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limonene gives rise to menthol, a flavoring agent and decongestant. GPP also supplies the 67

prenyl group in the biosynthesis of cannabinoids (Ahmed et al., 2015; Vickery et al., 68

2016), a class of natural products with promising pharmaceutical properties (Aizpurua-69

Olaizola et al., 2016). Sesquiterpenes (C15) are derived from FPP, itself generated through 70

condensation of GPP and isopentenyl pyrophosphate (IPP) in yeast or directly from IPP 71

and dimethylallyl pyrophosphate (DMAPP) units in plants. The sesquiterpene 72

amorphadiene gives rise to the antimalarial drug precursor artemisinic acid. The addition 73

of another IPP unit to FPP in yeast gives rise to GGPP, which forms the scaffold of the 74

diterpenes and diterpenoids (C20), such as taxadiene, a precursor to the taxane family of 75

chemotherapeutics. Condensation of two FPP units yields the linear triterpene squalene 76

(C30), which serves as the universal building block of all sterols, including ergosterol in 77

yeast. In plants, squalene gives rise to a number of pharmacologically active 78

triterpenoids, such as β-amyrin and lupeol. Tetraterpenes (C40) are produced through 79

condensation of two molecules of GGPP, yielding phytoene, the precursor to the 80

carotenoids, such as lycopene and β-carotene. Polyterpenes such as natural rubber (cis-81

polyisoprene) comprise thousands of isoprene units. 82

83

Alkaloids 84

In the broadest sense, alkaloids are defined as low-molecular-weight metabolites 85

containing heterocyclic (true alkaloids) or exocyclic (protoalkaloids, amines, and 86

polyamines) nitrogen atoms. Approximately 20,000 natural alkaloids are known, many of 87

which exhibit analgesic (morphine), stimulant (caffeine and ephedrine), psychotropic 88

(mescaline and cocaine), antibacterial (sanguinarine), anticancer (vinblastine and 89



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vincristine), antitussive (codeine), anti-inflammatory (berberine), antispasmodic 90

(papaverine), or antimalarial (quinine) activities. 91

Phenylalanine, tyrosine, and their derivatives (e.g., phenethylamine, tyramine, and 92

dopamine) are the source of a tremendous number of alkaloids, including the 93

benzylisoquinoline alkaloids (BIAs) and the phenethylisoquinoline alkaloids (Figure 2). 94

BIAs are a large class of roughly 2,500 metabolites that includes berberine, noscapine, 95

sanguinarine, and morphine. These important medicines are derived from the 96

condensation of dopamine and 4-hydroxyphenylacetaldehyde (4-HPAA), both of which 97

are synthesized from tyrosine. Dopamine can also condense with derivatives of 98

phenylalanine (4-hydroxydihydrocinnamaldehyde), yielding the phenethylisoquinoline 99

class of alkaloids. Phenylalanine and tyrosine form the basis of a number of simpler 100

protoalkaloids and catecholamines, including modified amphetamines (ephedrine and 101

cathinone), dopamine, mescaline, and adrenaline. Owing to the ubiquity of the indole 102

group in nature, tryptophan also forms the basis of many important alkaloids, such as 103

simple indoles, β-carbolines (serotonin and harmine), and the monoterpenoid indole 104

alkaloids (MIAs). 105

MIAs, derived from the condensation of the tryptophan analog tryptamine and a 106

monoterpenoid (secologanin), are one of the largest and most complex classes of 107

alkaloids, giving rise to more than 3,000 structures. The tryptophan precursor anthranilate 108

also serves as a precursor to several alkaloid sub-classes, including the quinazolines. 109

Beyond the aromatic amino acids, arginine and ornithine form the basis of the tropane, 110

pyrrolidine, pyrrolizidine, and pyridine alkaloids, whereas lysine is the precursor to the 111

piperidines and quinolizidines. Nucleosides also form the basis of some alkaloids, such as 112



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caffeine and theobromine. 113

114

Phenylpropanoids and polyketides 115

The phenylpropanoids represent a class of more than 8,000 plant phenolics derived from 116

tyrosine and phenylalanine via the phenylpropanoid pathway (Wu and Chappell, 2008). 117

The name phenylpropanoid refers to the distinctive C6-C3 structure of metabolites within 118

this pathway. The key phenylpropanoid branch point intermediate is p-coumaroyl-CoA 119

(Figure 3), which forms the basis of the flavonoids, stilbenoids, coumarins, lignans, 120

catechins, and aurones. In addition to the C6-C3 skeleton, the phenylpropanoid pathway 121

also diverts at the level of cinnamic or ferulic acid to yield an array of C6-C1 benzoates, 122

such as vanillin, benzaldehyde, and gallic acid (Vogt, 2010; Kallscheuer et al., 2019). 123

Although the stilbenoids and flavonoids originate from the phenylpropanoid pathway, 124

they are elongated by type III plant polyketide synthases (PKSs), underscoring the mixed 125

biosynthetic nature of these specialized metabolites (Box 1). PKSs accept CoA-bound 126

substrates (Yu et al., 2012), most often p-coumaroyl-CoA, although cinnamoyl- and 127

feruloyl-CoA form the basis of some phenylpropanoid polyketides, such as pinosylvin 128

and curcumin (Preisig-Müller et al., 1999; Kita et al., 2008). Once loaded with a starter 129

molecule, malonyl-CoA moieties are incorporated into the growing polyketide chain. 130

A number of different polyketide backbones can be produced, though the most 131

heavily targeted for metabolic engineering are the naringenin chalcone and resveratrol 132

scaffolds, which give rise to the respective flavonoid and stilbenoid subclasses (Lussier et 133

al., 2012). These compounds are functionalized in downstream reactions including 134

aromatic hydroxylation, nicotinamide adenine dinucleotide phosphate (NADPH)-135



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dependent reduction, O-methylation, and glycosylation. The flavonoids alone encompass 136

more than 6,000 natural products, including chalcones, aurones, catechins, flavanones, 137

flavanols, isoflavonoids, and anthocyanins (Yu et al., 2012). In contrast to the flavonoids 138

and stilbenoids, coumarins are not polyketides, as their lactone ring structure is derived 139

from hydroxylation, isomerization, and lactonization of phenolic acids (cinnamic, p-140

coumaric, caffeic, or ferulic acid) or the corresponding phenolic acyl-CoA esters (Kai et 141

al., 2008; Yao et al., 2017). 142

143

PIONEERING STUDIES IN THE MICROBIAL SYNTHESIS OF PLANT 144

METABOLITES 145

The most famous application of synthetic biology for the synthesis of valuable plant 146

products is semisynthetic artemisinin, an antimalarial terpenoid natively produced by 147

sweet wormwood (Artemisia annua). Over a period of more than a decade, artemisinic 148

acid production has reached titers of 25 g/L in yeast (Paddon et al., 2013), whereas 149

Escherichia coli has been engineered to produce 27 g/L of the amorphadiene precursor 150

(Tsuruta et al., 2009). The yeast artemisinic acid production strain has been repurposed as 151

a sesquiterpenoid platform, facilitating industrial-scale production of more than 130 g/L 152

farnesene (Meadows et al., 2016). Paclitaxel is another terpenoid medicine and microbes 153

have been engineered to produce up to 1 g/L of the taxadiene scaffold (Ajikumar et al., 154

2010; Ding et al., 2014; Zhou et al., 2015). Other notable terpenoid pathway 155

reconstructions include limonene, pinene, geraniol, eucalyptol, humulene, β-156

carophyllene, patchoulol, santalene, and bisabolene (Table 1). 157

Because geraniol forms half of the MIA scaffold, strategies successfully used to 158



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produce monoterpenoids were exploited to synthesize MIA intermediates in yeast, such 159

as nepetalactol (Campbell et al., 2016; Billingsley et al., 2017) and strictosidine (Brown 160

et al., 2015). These efforts have yet to be extended to the de novo synthesis of 161

functionalized MIAs in a microbial system, although impressive partial pathway 162

reconstructions have been reported (Qu et al., 2015). The BIA class has also recently 163

experienced several breakthrough microbial pathway reconstitutions. As a result of 164

successes in resolving upstream pathways involving conversion of tyrosine to dopamine, 165

de novo formation of (S)-reticuline was demonstrated for the first time (Nakagawa et al., 166

2011; DeLoache et al., 2015). This pathway was later extended for de novo biosynthesis 167

of morphinan alkaloids in E. coli and yeast (Galanie et al., 2015; Nakagawa et al., 2016), 168

as well as noscapine in yeast (Li et al., 2018). Titers of (S)-reticuline have recently been 169

increased to 160 mg/L in E. coli (Matsumura et al., 2018). Stilbenoids have been the 170

target of several microbial synthesis efforts and the de novo titer of resveratrol has 171

reached 5 g/L in yeast (Li et al., 2016; Katz et al., 2017). Other stilbenoids produced in 172

microbes include pinostilbene, pterostilbene, pinosylvin, and piceatannol (Table 1). 173

Similarly, the branch point flavonoid naringenin has been produced from glucose at titers 174

above 200 mg/L (Lehka et al., 2016). The flavonoid pathway has been diversified in E. 175

coli and yeast to yield the dihydrochalcone phloretin and its derivatives, the flavanone 176

liquiritigenin, and the flavonols kaempferol, quercetin, and fisetin, among others (Table 177

1). This pathway was recently extended to produce anthocyanin pigments using E. coli 178

polycultures (Jones et al., 2017) and a single engineered yeast strain (Eichenberger et al., 179

2018; Levisson et al., 2018). 180

Not all natural product syntheses involve straightforward maximization of product 181



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titer, as some applications require careful tuning of product concentrations. One such 182

study involved combinatorial engineering of industrial brewing yeasts (S. cerevisiae) to 183

generate strains with a diverse range of geraniol and linalool production profiles, 184

culminating in the formulation of beers with a more desirable hops flavor compared to 185

commercial varieties (Denby et al., 2018). Studies such as these highlight the wide range 186

of applications afforded through the manipulation of plant metabolic pathways in 187

microbial systems. 188

189

ELUCIDATION OF PLANT METABOLIC PATHWAYS 190

In planta 191

Traditionally, the elucidation of metabolic pathways in source plants has been the driving 192

force and often limiting factor of microbial biosynthesis. Owing to the complexity of 193

plant metabolism, gaps in pathways are common, particularly within downstream 194

reactions mediating the formation of functionalized products. Pathway gaps in the context 195

of microbial synthesis refer to a lack of enzyme identification, as the biochemical nature 196

of metabolic transformations is typically known. 197

To bypass gaps in enzyme elucidation, pathway intermediates are often supplied 198

to cells exogenously, granted they are available and an uptake system exists. Although 199

enzyme gaps have plagued many natural product pathways, a flurry of activity has 200

recently led to the completion of several important pathways. While it was known that 201

production of the nepetalactol backbone within the MIA pathway involved reductive 202

cyclization of 10-oxogeranial, the enzyme mediating this transformation was finally 203

discovered in 2012 (Geu-Flores et al., 2012). Critical to this success was the search of 204



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source plant transcriptomes for redox enzymes co-expressed with MIA pathway 205

transcripts. Other key enzymes within the early MIA pathway were discovered in 2014 206

(Miettinen et al., 2014), prompting the synthesis of the key branch point MIA 207

strictosidine in yeast soon thereafter (Brown et al., 2015). 208

The MIA pathway leading to vinblastine was fully elucidated in 2018 (Caputi et 209

al., 2018); thus, it is only a matter of time before the de novo synthesis of this potent 210

anticancer medicine is achieved in a microbial system. Similarly, the final enzymes 211

involved in the formation of substituted amphetamines, such as ephedrine and 212

pseudoephedrine (Hagel et al., 2012), were also identified as of 2018 (Morris et al., 213

2018), providing rationale for their synthesis in a microbial system. The opium poppy 214

(Papaver somniferum) enzyme responsible for the stereochemical inversion of (S)- to (R)-215

reticuline eluded identification for many years, limiting morphine pathway 216

reconstructions to upstream [glucose to (S)-reticuline] and downstream [(R)-reticuline to 217

morphine] modules. Eventual identification of the fusion enzyme by three research 218

groups led to the reconstruction of the de novo morphinan pathway within a microbial 219

host (Galanie et al., 2015). Candidate epimerase genes were identified using 220

transcriptome database mining and candidates were silenced in opium poppy plants, 221

sequenced from mutants that accumulate (S)-reticuline, or cloned in S. cerevisiae for 222

functional analysis (Farrow et al., 2015; Galanie et al., 2015; Winzer et al., 2015). While 223

this sequence of events permeates the field of microbial synthesis, in which pathway 224

elucidation in planta precedes pathway reconstruction in microbes, a recent paradigm has 225

arisen in response to this laborious and time-consuming process. 226

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In microbes 228

Due to the declining cost of DNA synthesis, rapidly advancing bioinformatics tools, and 229

expanding omics databases, it has become possible to resolve single and multi-enzyme 230

gaps within a heterologous microbial host. Using this synthetic biology approach, 231

libraries of candidate gap-filling enzymes are first compiled by querying plant 232

transcriptome databases, such as 1000 Plants (Matasci et al., 2014) or PhytoMetaSyn 233

(Xiao et al., 2013) Projects. The corresponding genes are then codon-optimized, 234

synthesized, and expressed in a laboratory microbe. This workflow facilitates the 235

resolution of enzyme gaps in plant metabolic pathways without having to obtain physical 236

plant material or cDNAs (Narcross et al., 2016). In this regard, synthetic biologists do not 237

need to wait for gap-filling enzymes to be isolated and characterized from natural sources 238

to reconstitute target pathways in a microbial species. One of the groups involved in 239

identifying the aforementioned reticuline epimerase gene employed this strategy by 240

querying plant transcriptome databases and integrating synthetic genes into a yeast strain 241

harboring a downstream module for thebaine synthesis (Galanie et al., 2015). An 242

ambitious combinatorial variation of this technique was attempted to fill a seven-enzyme 243

gap within the vinblastine MIA pathway (Casini et al., 2018). While the authors were 244

unable to resolve this intricate pathway, they succeeded in building 74 strains, each 245

possessing a distinct combination of the seven gene candidates. This study illustrates the 246

immense potential of synthetic biology for elucidating and reconstructing complex 247

biochemical pathways in microbial systems. 248

249

HOST SELECTION 250



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Host selection is a fundamental facet of microbial synthesis and a key determinant of 251

pathway performance. Since it is virtually impossible to forecast the ideal host for 252

synthesizing a target metabolite, a number of factors must be weighed, including access 253

to a complete genome sequence and the availability of genetic tools. Precursor 254

availability is perhaps the most important criterion of host selection, as an abundant 255

precursor pool, such as acetyl-CoA or shikimate, sidesteps the need to rewire core 256

metabolism. Host selection is further complicated by the existence of phenotypically 257

distinct strains within a given species, for instance the E. coli K and B lineages or the 258

S288C and CEN.PK strains of S. cerevisiae. In a dramatic instance, utilization of E. coli 259

DH1 improved oxidation of amorphadiene by a factor of 1,000 relative to related strains 260

(Chang et al., 2007). Screening of E. coli lineages for polyketide synthesis has revealed 261

not only strain-specific differences in baseline polyketide production but also differences 262

in response to the same genetic manipulations (Yang et al., 2018). Due to differences in 263

amino acid biosynthesis between S. cerevisiae (Canelas et al., 2010), production of 264

vanillin-β-glucoside was significantly higher in S288C than in CEN.PK (Strucko et al., 265

2015). Similar yeast-specific differences were observed for the synthesis of the 266

polyketide triacetic acid lactone (Saunders et al., 2015). These studies highlight the often 267

overlooked task of screening strains to identify optimal producers prior to 268

comprehensively engineering a production strain. 269

270

Workhorses and specialized hosts 271

To date, the overwhelming majority of microbial syntheses have employed E. coli or S. 272

cerevisiae owing to their ease of genetic and metabolic manipulation, a comprehensive 273



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understanding of their genetics, metabolism, and physiology, and their highly active 274

central metabolic pathways. Several critical differences between these industry-proven 275

hosts inform many microbial synthesis campaigns (Box 2). 276

Recently, the diversity of microbial hosts exploited for the synthesis of plant 277

natural products has expanded dramatically. Some microorganisms naturally synthesize 278

aromatic amino acids at levels well above those of E. coli and S. cerevisiae, indicating a 279

major potential of these hosts for the production of alkaloids and phenylpropanoids. Of 280

particular importance is Corynebacterium glutamicum, an industrial bacterium with a 281

tremendous capacity to synthesize glutamate and lysine, as well as aromatic amino acids 282

(Azuma et al., 1993; Ikeda et al., 1993). Lactococcus lactis is another industry-proven 283

bacterium with a demonstrated capacity to synthesize plant terpenoids and 284

phenylpropanoids (Gaspar et al., 2013; Dudnik et al., 2018). The yeast Scheffersomyces 285

stipitis has gained interest for its ability to utilize C5 sugars, suggesting that this organism 286

has a more active pentose phosphate pathway than does S. cerevisiae. Indeed, the highest 287

shikimate titer reported to date in yeast was achieved using S. stipites (Gao et al., 2016). 288

Within the polyketide class of natural products, bacteria from the genus 289

Streptomyces are major natural producers, providing rationale for diverting these native 290

pathways to plant-derived polyketides (Baltz, 2010). The oleaginous yeast Yarrowia 291

lipolytica has also been demonstrated to be a promising host for terpenoids, polyketides, 292

and other compounds derived from acetyl-CoA (Abdel-Mawgoud et al., 2018). Other 293

hosts are desirable for superior growth characteristics, such as Pichia pastoris, a yeast 294

that attains higher cell densities than S. cerevisiae (Wriessnegger et al., 2014). 295

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RECONSTITUTION AND OPTIMIZATION OF PLANT PATHWAYS IN 297

MICROBIAL SYSTEMS 298

Pathway assembly and delivery 299

Pathway assembly refers to the design and organization of genetic parts required to 300

reconstruct heterologous pathways in microbes. This endeavor begins by selecting and 301

synthesizing gene variants responsible for mediating the synthesis of the target product. 302

The selected candidates are placed within transcriptional units containing a promoter and 303

terminator. Traditionally, heterologous genes and metabolic pathways have been 304

delivered and expressed from plasmids. While this technique has certain merits, such as 305

facilitating the rapid screening of prospective hosts (Casini et al., 2018) and easily 306

assessing the performance of pathway modules (Fossati et al., 2014), access to efficient 307

genome editing tools has led to the adoption of chromosomal expression systems 308

(Horwitz et al., 2015; Jakočiūnas et al., 2015). Furthermore, plasmid-borne expression 309

leads to significant variability in gene expression and copy number between cells (Ryan 310

et al., 2014). 311

With respect to transcriptional control, most pathways are assembled by placing 312

all genes under control of constitutive promoters. For instance, amorphadiene and 313

artemisinic acid production strains were first constructed using galactose induction, 314

which was later converted to constitutive expression without affecting production or 315

fitness (Westfall et al., 2012; Paddon et al., 2013). Because even “constitutive” promoters 316

exhibit distinct transcriptional profiles, which vary based on carbon source or medium 317

formulation (Reider Apel et al., 2016), major efforts have focused on comprehensively 318

characterizing both promoter and terminator elements (Yamanishi et al., 2013; Lee et al., 319



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2015). These toolkits facilitate the exploration of vast pathway design spaces comprised 320

of a staggering number of possible gene and expression combinations. 321

Product titer, rate, and yield following initial pathway reconstitution are often 322

very poor, necessitating many design-build-test engineering cycles to reach 323

commercially-viable levels. Historically, this process lasts 6-8 years and costs more than 324

$50 million (Nielsen and Keasling, 2016). These metrics are declining at a dramatic rate 325

as a result of the standardization of synthetic biology and the advent of high-throughput 326

strain engineering facilities (‘biofoundries’), which aim to miniaturize and automate 327

strain construction workflows (Chao et al., 2017; Casini et al., 2018). 328

329

Expression of plant genes in microbial species 330

The functional expression of plant genes in microbial species poses a number of technical 331

challenges. Many plant enzymes possess localization signals for targeting to specific 332

organelles, such as the chloroplast. Implementation of these plant genes in microbial 333

hosts typically leads to poor gene expression or insolubility of the corresponding protein 334

(Williams et al., 1998). Most terpene synthases are plastid-localized and thus N-terminal 335

truncation is an effective strategy for improving activity (Alonso-Gutierrez et al., 2013; 336

Zhao et al., 2016). Production of BIAs is also improved through N-terminal truncation of 337

norcoclaurine synthase (Li et al., 2016). While software tools exist for predicting optimal 338

signal peptide cleavage sites (Petersen et al., 2011), assessing various-sized truncations 339

affords a range of improvements (Nishihachijo et al., 2014; Jiang et al., 2017). 340

Perhaps the most challenging facet of synthesizing plant-derived metabolites in 341

microbial hosts is the functional expression of cytochrome P450 (CYP) enzymes. This 342



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obstacle provides much of the rationale for using eukaryotic expression systems over 343

bacteria (Box 2). CYPs are membrane-bound enzymes that carry out many of the 344

complex functionalizations in secondary metabolic pathways, including hydroxylations, 345

double bond epoxidations, and dealkylations (Meunier et al., 2004). Because CYPs 346

mediate oxidation reactions, catalysis is coupled to reduction of NADPH, which in turn 347

requires a cytochrome P450 reductase (CPR) partner to shuttle electrons between 348

NADPH and CYP. Additional components can also be involved, such as cytochrome b5 349

and a cytochrome b5 reductase (Porter, 2002; Paddon et al., 2013; Li et al., 2016). 350

Some species of plant contain hundreds of CYPs and multiple CPRs, leading to 351

immense challenges in optimizing heterologous CYP-CPR pairings. Although yeast 352

contains a native CPR, most plant CYPs exhibit greater activity when paired with CPRs 353

from the same plant species (Fossati et al., 2014). Production of highly functionalized 354

secondary metabolites, such as paclitaxel and hydrocodone, involves numerous CYP-355

catalyzed reactions, requiring the coordinated expression of multiple CPR genes. To 356

overcome this hurdle, most microbial synthesis studies employ a “one-size-fits-all” 357

strategy by pairing multiple CYPs with a single CPR. CYP and CPR expression must be 358

carefully balanced to ensure efficient shuttling of electrons and avoid the production of 359

toxic reactive oxygen species. Optimization of CYP-CPR pairing was paramount to the 360

success of the semi-synthetic artemisinin process (Paddon et al., 2013) and enabled 361

production of 500 mg/L oxygenated taxadiene in E. coli (Biggs et al., 2016). 362

The most efficient natural CYP is a primitive bacterial CYP-CPR fusion from 363

Bacillus megaterium (Munro et al., 2002). This architecture has been exploited for the 364

expression of plant CYPs in E. coli, in which the N-terminal membrane-binding domain 365



16

is cleaved or modified for more efficient insertion within bacterial membranes (Hausjell 366

et al., 2018). Conversely, it has been shown that a direct CYP-CPR fusion in E. coli was 367

less active than carefully balanced expression of both components for oxygenated 368

taxadiene synthesis (Biggs et al., 2016). The authors suggest that since plant CYPs and 369

CPRs do not interact in a 1:1 ratio, a direct fusion approach is not appropriate. 370

371

Precursor supply 372

Engineering microbial systems for the production of phenylpropanoids and most 373

alkaloids demands an abundant supply of aromatic amino acid precursors (Figure 2 and 374

Figure 3). Tremendous strides have been made in engineering platform strains producing 375

high levels of tyrosine, phenylalanine, tryptophan, and their derivatives (Table 1). 376

Deregulating host precursor pathways is regarded as the chief hurdle to the 377

production of heterologous metabolites (Nielsen and Keasling, 2016). The yeast 378

shikimate and aromatic amino acid pathways are subject to multiple layers of 379

transcriptional and post-transcriptional control. The entry point to the shikimate pathway 380

involving condensation of E4P and PEP is catalyzed by 3-deoxy-D-arabino-381

heptulosonate-7-phosphate (DAHP) synthase, for which two isoenzymes exist in yeast 382

(Aro3 and Aro4). Allosteric inhibition by tyrosine can be overcome in both enzymes 383

using analogous mutations (Aro3K222L

and Aro4K229L

) (Luttik et al., 2008; Brückner et al., 384

2018). Similarly, chorismate mutase (Aro7) is feedback-inhibited by tyrosine, prompting 385

discovery of the Aro7G141S

allele for deregulating tyrosine biosynthesis (Luttik et al., 386

2008). Implementation of Aro4K229L

and Aro7G141S

in the same host leads to a 200-fold 387

increase in extracellular levels of aromatic compounds. 388



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The terpenoid branch of secondary metabolism has also been the focal point of 389

engineering precursor supply. The rate-limiting step of the mevalonate pathway catalyzed 390

by HMG-CoA reductase (HMGR) can be improved by implementing a truncated mutant 391

(tHMGR). Owing to the importance of this enzymatic step, studies achieving high-level 392

terpenoid or MIA production have incorporated up to four gene copies of tHMGR 393

(Paddon et al., 2013; Brown et al., 2015). 394

The production of GPP-derived monoterpenoids poses a unique engineering 395

challenge pertaining to the dual nature of the yeast Erg20 protein. This enzyme catalyzes 396

the synthesis of GPP from IPP and DMAPP, as well as the subsequent condensation of 397

GPP and an additional unit of IPP to give FPP (Figure 1). Owing to the central role of 398

FPP in ergosterol biosynthesis, Erg20 is an essential enzyme, signifying that its FPP 399

synthase activity can not be abolished. Instead, Erg20 variants with reduced GPP-binding 400

properties have been described (Chambon et al., 1990) and exploited for the production 401

of various monoterpenoids and MIAs (Brown et al., 2015; Campbell et al., 2016). 402

Relatedly, the essential squalene synthase enzyme (Erg9) generates squalene from two 403

FPP units, thus placing constraints on the production of all terpenoids deriving from FPP 404

(Figure 1). 405

The most fundamental means of circumventing host regulation is replacing native 406

precursor pathways with a heterologous counterpart. This approach was utilized in early 407

efforts to produce amorphadiene in E. coli, wherein the native MEP pathway was 408

replaced by the yeast mevalonate pathway (Martin et al., 2003). Reconstructing the yeast 409

pathway within a bacterial operon eliminates both E. coli and S. cerevisiae modes of 410

regulation, facilitating constitutive production of terpenoids. 411



18

Acetyl-CoA plays a pivotal role in the biosynthesis of terpenoids, polyketides, 412

phenylpropanoids, and cannabinoids (Figure 1 and Figure 3), and its overproduction has 413

also been a target for improvement. In yeast, multiple acetyl-CoA synthesis pathways 414

exist in different subcellular compartments, which acetyl-CoA can not directly cross 415

(Strijbis and Distel, 2010). This provides options for strain engineering based on the 416

pathway that is most suited for a particular heterologous product (van Rossum et al., 417

2016). Alternatively, heterologous cytosolic acetyl-CoA pathways are of great interest 418

(Kozak et al., 2014; Kozak et al., 2014; Zhang et al., 2015; Cardenas and Da Silva, 2016; 419

Kozak et al., 2016; Meadows et al., 2016; Rodriguez et al., 2016). The highest reported 420

titer of a heterologous product derived from cytosolic acetyl-CoA is the synthesis of 130 421

g/L of the sesquiterpene farnesene under fermentative conditions (Meadows et al., 2016). 422

This approach utilized multiple alternative cytosolic acetyl-CoA pathways to overproduce 423

farnesene. 424

In prokaryotes, all routes to acetyl-CoA are equally accessible, reducing the 425

necessity for alternative pathways, although they have been demonstrated (Wang et al., 426

2018). However, buildup of acetyl-CoA results in its conversion to acetate, which is an 427

unproductive carbon sink. In E. coli, native acetate assimilation enzymes can be 428

overexpressed to convert acetate back to acetyl-CoA, resulting in improved flavanone 429

biosynthesis (Leonard et al., 2007; Zha et al., 2009). Gene knockouts have been identified 430

that prevent acetate synthesis and improve heterologous production without reducing 431

cellular fitness (Zha et al., 2009; Liu et al., 2017). Eliminating pathway bottlenecks to 432

improve flux through acetyl-CoA can also reduce acetate overflow (Li et al., 2015; King 433

et al., 2017; Wang et al., 2018). Relatively little attention has been placed on the 434



19

availability of free Coenzyme A to accept increased carbon flux. Supplementation of the 435

Coenzyme A precursor pantothenate can improve the yield of heterologous products 436

requiring acetyl-CoA. Several studies have demonstrated that overexpression of the rate-437

limiting step of Coenzyme A synthesis, pantothenate kinase, improves product synthesis 438

two-fold (Fowler et al., 2009; Schadeweg and Boles, 2016; Liu et al., 2017). 439

Phenylpropanoid, polyketide and cannabinoid synthesis require malonyl-CoA, 440

which is used for fatty acid biosynthesis in E. coli and S. cerevisiae. In these organisms, 441

fatty acid synthesis is tightly-regulated (Davis et al., 2000). Improving synthesis and 442

reducing off-target consumption of malonyl-CoA are the major areas for overproduction. 443

Acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase (Acc) and 444

improvements in this activity have been achieved by overexpression (Zha et al., 2009; Xu 445

et al., 2011; Yang et al., 2018), ablating post-translational modification sites (Choi and 446

Da Silva, 2014; Shi et al., 2014; Chen et al., 2018), and improving the availability of its 447

biotin cofactor (Leonard et al., 2007). Acc-independent malonyl-CoA synthesis has also 448

been demonstrated (Leonard et al., 2008), though the pathway requires supplemented 449

malonate. Reducing the diversion of malonyl-CoA to essential pathways is a challenge, 450

because fatty acids are required for biomass production. In yeast, knockout of genes 451

regulating fatty acid biosynthesis improved titers of malonyl-CoA-derived products (Zha 452

et al., 2009; Chen et al., 2017), yet the strain was auxotrophic for inositol. More 453

promisingly, biomass accumulation prior to conditional gene knockdown has been 454

demonstrated to improve polyketide titers in E. coli (Yang et al., 2015; Liang et al., 2016; 455

Wu et al., 2016; Yang et al., 2018). 456



20

As a ubiquitous cofactor and the source of reductant for plant CYPs, NADPH is 457

an important engineering target for the synthesis of natural products. A proven strategy 458

for enhancing NADPH availability is the inactivation of native NADPH-consuming 459

reactions. A caveat of this approach pertains to the targeting of enzymes involved in 460

central carbon metabolism, such as glucose-6-phosphate isomerase (Pgi) and 461

phosphoenolpyruvate carboxylase (Ppc) in E. coli (Chemler et al., 2010) or glucose-6-462

phosphate dehydrogenase (Zwf1) in S. cerevisiae (Gold et al., 2015). Glutamate 463

dehydrogenase (GldH or Gdh1) is a promising candidate in both species (Asadollahi et 464

al., 2009; Chemler et al., 2010). Inactivation of these central targets often has deleterious 465

effects on strain fitness, including the generation of amino acid auxotrophy (Gold et al., 466

2015), demanding a delicate balancing of core pathways and sophisticated metabolic 467

models for predicting combinatorial modifications (Chemler et al., 2010). 468

The counter approach of upregulating NADPH-generating enzymes is a more 469

viable avenue for engineering NADPH supply. In yeast, these enzymes include 470

prephenate dehydrogenase (Tyr1) and cytosolic aldehyde dehydrogenase (Ald6) (Li et al., 471

2018). Curiously, both overexpression and deletion of ZWF1 have been shown to 472

enhance formation of tyrosine products (Gold et al., 2015; Li et al., 2018), underscoring 473

the complexity of yeast central metabolism and redox homeostasis. 474

475

Improving flux to heterologous pathways 476

Flux improvement involves iterative rounds of strain engineering with the aim of 477

elevating product titer, rate, and yield. Efforts to improve flux through a target pathway 478

begin with the identification of rate-limiting enzymatic conversions, which is diagnosed 479



21

by monitoring levels of pathway intermediates. The most fundamental means of relieving 480

metabolic bottlenecks is to increase levels of rate-limiting enzymes by increasing gene 481

expression or copy number. In addition to high-level expression of the heterologous 482

pathway, the entire eight-gene yeast pathway from acetyl-CoA to FPP was overexpressed 483

in the industrial artemisinic acid strain (Paddon et al., 2013). 484

Poor pathway flux can also arise from the diversion of pathway intermediates to 485

off-target routes, either by host activities or promiscuous plant enzymes. Because 486

phenylpropanoid biosynthesis derives from phenylalanine or tyrosine, the yeast pathway 487

for aromatic amino acid degradation (Ehrlich pathway) is typically inactivated through 488

deletion of amino acid decarboxylase genes (ARO10 and PDC5) (Rodriguez et al., 2015). 489

Yeast BIA biosynthesis involves a more intricate balancing of tyrosine pathways, as the 490

dopamine and 4-HPAA precursors are derived from its biosynthesis and degradation, 491

respectively (Narcross et al., 2016). The physiological fate of 4-HPAA in yeast involves 492

conversion to tyrosol or 4-hydroxyphenylacetate, which can be mediated by more than 20 493

candidate enzymes (Hazelwood et al., 2008; DeLoache et al., 2015). These enzymes have 494

also been implicated in the irreversible reduction of aldehyde intermediates within the 495

MIA pathway (Billingsley et al., 2017), suggesting that any pathway possessing carbonyl 496

intermediates is subject to diversion by host activities. In a similar scenario, a yeast 497

reductase was shown to divert p-coumaroyl-CoA within the phenylpropanoid pathway to 498

an unwanted side product (Lehka et al., 2016). 499

Pathway flux can also be diverted to off-target routes by heterologous pathway 500

enzymes. O- and N-methyltransferases within the core BIA pathway have been shown to 501

exhibit a wide substrate range (Frick et al., 2001; Ounaroon et al., 2003; Fossati et al., 502



22

2014), which was circumvented by screening of plant homologues for variants exhibiting 503

a more stringent substrate specificity (Narcross et al., 2016). In addition to catalyzing the 504

reductive cyclization of 10-oxogeranial, iridoid synthase within the MIA pathway was 505

found to exhibit activity on other intermediates (Campbell et al., 2016). In this case, 506

enzyme activity was higher on the unwanted substrates than the physiological substrate. 507

Enzyme promiscuity may be avoided in co-cultures, in which a pathway is split 508

between strains such that promiscuous enzymes are sequestered from pathway 509

intermediates (Nakagawa et al., 2014). Loss of intermediates is also mitigated through 510

enzyme fusion, as in the cases of geraniol synthase or patchoulol synthase through fusion 511

to yeast farnesyl diphosphate synthase (Erg20) (Albertsen et al., 2011; Jiang et al., 2017). 512

Fusions have the potential to facilitate more efficient substrate channeling by maintaining 513

close physical proximity of sequential pathway enzymes, thus limiting competition from 514

host enzymes. In addition to terpenoid systems, fusion of resveratrol biosynthetic 515

enzymes facilitated a 15-fold improvement in titer in engineered S. cerevisiae (Zhang et 516

al., 2006). Enzyme fusions have the added potential to improve protein stability or 517

solubility, as demonstrated through fusions of taxadiene synthase with the soluble E. coli 518

maltose binding protein, yielding a 25-fold improvement in taxadiene titer (Reider Apel 519

et al., 2016). Fusions with maltose-binding protein also improved production of α-ionone 520

up to 50-fold (Zhang et al., 2018). 521

522

EXPANDING THE PLANT SECONDARY METABOLIC SPACE IN 523

MICROBIAL SYSTEMS 524

An emerging application of synthetic biology aims to exploit microbial systems for drug 525



23

discovery. In this manner, plant enzyme promiscuity and combinatorial biochemistry are 526

exploited to synthesize new structural scaffolds and functionalizations not found in 527

nature. 528

A common chemical modification within the pharmaceutical industry is 529

halogenation, in which fluoro or chloro moieties are introduced to drug candidates to 530

modify the physicochemical properties of the compound. Because many natural products 531

derive from amino acids, halogenated analogs can be supplemented to engineered 532

microbes leading to the formation of halogenated products. This strategy was used to feed 533

yeast fluoro- or chloro-tyrosine, resulting in the synthesis of halogenated BIA pathway 534

intermediates (Li et al., 2018). Halogenated end products were not detected, suggesting a 535

more stringent substrate specificity of downstream BIA enzymes. Moreover, this method 536

relies on the supplementation of costly amino acid analogs and could be overcome by 537

engineering de novo production of halogenated BIAs. 538

O-sulphated reticuline has been produced de novo by implementing a human 539

sulphotransferase into E. coli engineered for reticuline biosynthesis (Matsumura et al., 540

2018). Promiscuity of BIA pathway enzymes has also been exploited for the production 541

of novel scaffolds, such as disubstituted- and spiro-tetrahydroisoquinolines, by harnessing 542

the capacity of norcoclaurine synthase to accept an exceptional range of carbonyl 543

substrates (Lichman et al., 2017). Again, this strategy relies on the supplementation of 544

costly substrates, in this case carbonyl species that are not synthesized by 545

microorganisms. Moving these in vitro assays to robust de novo biosynthetic processes 546

presents a formidable challenge. 547

548



24

CONCLUDING REMARKS 549

Microbial synthesis provides a new avenue for the production of natural plant 550

pharmaceuticals, fragrances, nutrients, and colorants. Although this field is in its infancy 551

and faces many challenges (see Outstanding Questions), the wealth of successes in recent 552

years has solidified microbial biosynthetic production as a viable alternative to natural 553

product extraction and total chemical synthesis. The elucidation of increasingly complex 554

plant secondary pathways continues to drive the reconstruction of longer and more 555

challenging routes in microbial systems. Indeed, the discovery of missing enzymes in 556

several highly sought-after plant specialized pathways has primed a number of untapped 557

natural products for de novo biosynthesis in a microbial species. Several microbially-558

derived natural products have reached commercialization and these successes will 559

continue to pave the way for new opportunities. The exploitation of microbial systems for 560

drug discovery promises to deliver important new structural scaffolds and chemical 561

functionalizations that have hitherto not been observed in nature. 562



25

563

ACKNOWLEDGMENTS 564

This work was supported financially by a NSERC-Industrial Biocatalysis Network (IBN) grant, 565

and a NSERC Discovery grant. M.E.P. is supported by a NSERC postdoctoral fellowship, and 566

L.N. is supported by a FQRNT DE Doctoral Research Scholarship for Foreign Students. V.J.J.M. 567

is supported by a Concordia University Research Chair. 568



26

Table 1 – Selection of de novo plant secondary pathway reconstructions in microbial systems 569

Titer (mg/L)

Metabolite class Metabolite S. cerevisiae E. coli Reference(s)

PRECURSORS tyrosine 1,930a 55,000 (Patnaik et al., 2008)

p-coumaric acid 1,930 2,510 (Rodriguez et al., 2015; Jones et al., 2017)

dopamine 24 2,150 (Nakagawa et al., 2014; DeLoache et al., 2015)

TERPENOIDS Monoterpenoids

geraniol 1,680 2,000 (Liu et al., 2016; Jiang et al., 2017)

pinene ND 970 (Yang et al., 2013)

limonene 0.49 2,700 (Willrodt et al., 2014; Jongedijk et al., 2015)

eucalyptol 400 653 (Ignea et al., 2011; Mendez‐Perez et al., 2017)

linalool 0.75 505 (Mendez‐Perez et al., 2017; Camesasca et al.,

2018)

Sesquiterpenoids

β-farnesene 130,000 8,700 (Meadows et al., 2016; You et al., 2017)

bisabolene 5,200 912 (Peralta-Yahya et al., 2011; Özaydın et al., 2013)

α-humulene 1,300 ND (Zhang et al., 2018)

β-caryophyllene ND 1,520 (Yang et al., 2016)

amorphadiene 37,000 27,400 (Tsuruta et al., 2009; Westfall et al., 2012)

artemisinic acid 25,000 ND (Paddon et al., 2013)

santalene 163 ND (Tippmann et al., 2016)

patchoulol 40.9 ND (Albertsen et al., 2011)



27

Diterpenoids

jolkinol C 800 ND (Wong et al., 2018)

taxadiene 72.8 1,020 (Ajikumar et al., 2010; Ding et al., 2014)

Triterpenoids

β-amyrin 108.1 NR (Takemura et al., 2017; Zhu et al., 2018)

Tetraterpenoids

β-carotene 162.1 3,200 (Yang and Guo, 2014; Wang et al., 2016)

lycopene 1,650 3,520 (Sun et al., 2014; Chen et al., 2016)

ALKALOIDS Benzylisoquinoline

alkaloids

(S)-reticuline 0.082 160 (DeLoache et al., 2015; Matsumura et al., 2018)

thebaine 0.0064 2.1 (Galanie et al., 2015; Nakagawa et al., 2016)

hydrocodone 0.0003 0.36 (Galanie et al., 2015; Nakagawa et al., 2016)

noscapine 2.2 ND (Li et al., 2018)

Monoterpene indole

alkaloids

strictosidine 0.5 ND (Brown et al., 2015)

PHENYLPROPANOIDS Stilbenoids

resveratrol > 5,000 51.8 (Katz et al., 2017; Yang et al., 2018)

pinostilbene 5.52 ~2.5 (Kang et al., 2014; Li et al., 2016)

pterostilbene 34.93 33.6 (Li et al., 2016; Heo et al., 2017)

pinosylvin 130.02 281 (Katz et al., 2017; Wu et al., 2017)



28

Flavonoids

naringenin >200 103.8 (Lehka et al., 2016; Yang et al., 2018)

scutellarin 108 ND (Liu et al., 2018)

genistein 7.7 ND (Trantas et al., 2009)

pinocembrin 2.6 432.4 (Wu et al., 2016; Eichenberger et al., 2017)

quercetin 20.38 ND (Rodriguez et al., 2017)

kaempferol 66.29 57b (Yang et al., 2014; Duan et al., 2017)

dihydrokaempferol 44 ND (Levisson et al., 2018)

pelargonidin-3-O-

glucoside 0.02 9.5 (Jones et al., 2017; Levisson et al., 2018)

phloretin 42.7 ND (Eichenberger et al., 2017)

Coumarins

umbelliferone ND 66.1 (Yang et al., 2015)

esculetin ND 61.4 (Yang et al., 2015)

4-hydroxycoumarin ND 483.1 (Lin et al., 2013) atiter reported for the downstream metabolite p-coumaric acid 570

btiter reported for kaempferol 3-O-rhamnoside 571

ND: no data available 572 NR: titer not reported 573



29

Figure legends 574

Figure 1. Interfacing plant terpenoid secondary metabolic pathways with microbial 575

metabolism. Plant secondary metabolic reactions and pathways (green) are shown linked 576

to core microbial metabolism (beige shading; black font). S. cerevisiae is shown as the 577

prospective host species. Key yeast enzymes discussed in the main text are shown. 578

Abbreviations: Bts1, geranylgeranyl diphosphate synthase; DMAPP, dimethylallyl 579

pyrophosphate; Erg9, squalene synthase; Erg20, farnesyl pyrophosphate synthetase; FPP, 580

farnesyl pyrophosphate; GPP, geranyl pyrophosphate; GGPP, geranylgeranyl 581

pyrophosphate; IPP, isopentenyl pyrophosphate; MEV, mevalonate pathway. 582

583

Figure 2. Interfacing plant alkaloid secondary metabolic pathways with microbial 584

metabolism. S. cerevisiae is shown as the prospective host species. Refer to Figure 1 for 585

abbreviations and color coding. Additional abbreviations: AAA path, aromatic amino 586

acid pathway; Aro1, pentafunctional arom protein; Aro2, chorismate synthase and Flavin 587

reductase; Aro3+Aro4, DAHP synthase isoenzymes; Aro7, chorismate mutase; E4P, 588

erythrose 4-phosphate; 4-HPAA, 4-hydroxyphenylacetaldehyde; R5P, ribose 5-589

phosphate; PPP, pentose phosphate pathway; PEP, phosphoenolpyruvate; TCA cycle, 590

tricarboxylic acid cycle. 591

592

Figure 3. Interfacing plant phenylpropanoid and polyketide secondary metabolic 593

pathways with microbial metabolism. A selection of natural plant pathways in a 594

prospective S. cerevisiae host is shown. More extensive networks of natural and synthetic 595

phenylpropanoid routes have been shown previously (Wang et al., 2015; Zhao et al., 596

2015). Refer to Figure 1 and Figure 2 for abbreviations and color coding. Additional 597



30

abbreviations: Acc1, acetyl-CoA carboxylase; PAL, phenylalanine ammonia-lyase; TAL, 598

tyrosine ammonia-lyase; PKS, polyketide synthase. 599

600

LITERATURE CITED 601

Abdel-Mawgoud AM, Markham KA, Palmer CM, Liu N, Stephanopoulos G, Alper 602 HS (2018) Metabolic engineering in the host Yarrowia lipolytica. Metabolic 603 Engineering (in press) 604

Ahmed SA, Ross SA, Slade D, Radwan MM, Khan IA, ElSohly MA (2015) Minor 605 oxygenated cannabinoids from high potency Cannabis sativa L. Phytochemistry 606 117: 194-199 607

Aizpurua-Olaizola O, Soydaner U, Ozturk E, Schibano D, Simsir Y, Navarro P, 608 Etxebarria N, Usobiaga A (2016) Evolution of the cannabinoid and terpene 609 content during the growth of Cannabis sativa plants from different chemotypes. 610 Journal of Natural Products 79: 324-331 611

Ajikumar PK, Xiao W-H, Tyo KE, Wang Y, Simeon F, Leonard E, Mucha O, Phon 612 TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoid pathway optimization for 613 Taxol precursor overproduction in Escherichia coli. Science 330: 70-74 614

Albertsen L, Chen Y, Bach LS, Rattleff S, Maury J, Brix S, Nielsen J, Mortensen 615 UH (2011) Diversion of flux toward sesquiterpene production in Saccharomyces 616 cerevisiae by fusion of host and heterologous enzymes. Applied and 617 Environmental Microbiology 77: 1033-1040 618

Alonso-Gutierrez J, Chan R, Batth TS, Adams PD, Keasling JD, Petzold CJ, Lee TS 619 (2013) Metabolic engineering of Escherichia coli for limonene and perillyl 620 alcohol production. Metabolic Engineering 19: 33-41 621

Asadollahi MA, Maury J, Patil KR, Schalk M, Clark A, Nielsen J (2009) Enhancing 622 sesquiterpene production in Saccharomyces cerevisiae through in silico driven 623 metabolic engineering. Metabolic Engineering 11: 328-334 624

Azuma S, Tsunekawa H, Okabe M, Okamoto R, Aiba S (1993) Hyper-production of l-625 trytophan via fermentation with crystallization. Applied Microbiology and 626 Biotechnology 39: 471-476 627

Baltz RH (2010) Streptomyces and Saccharopolyspora hosts for heterologous expression 628 of secondary metabolite gene clusters. Journal of Industrial Microbiology & 629 Biotechnology 37: 759-772 630

Becker JV, Armstrong GO, van der Merwe MJ, Lambrechts MG, Vivier MA, 631 Pretorius IS (2003) Metabolic engineering of Saccharomyces cerevisiae for the 632 synthesis of the wine-related antioxidant resveratrol. FEMS Yeast Research 4: 79-633 85 634

Biggs BW, Lim CG, Sagliani K, Shankar S, Stephanopoulos G, De Mey M, 635 Ajikumar PK (2016) Overcoming heterologous protein interdependency to 636 optimize P450-mediated Taxol precursor synthesis in Escherichia coli. 637 Proceedings of the National Academy of Sciences: 201515826 638



31

Billingsley JM, DeNicola AB, Barber JS, Tang M-C, Horecka J, Chu A, Garg NK, 639 Tang Y (2017) Engineering the biocatalytic selectivity of iridoid production in 640 Saccharomyces cerevisiae. Metabolic Engineering 44: 117-125 641

Brown S, Clastre M, Courdavault V, O’Connor SE (2015) De novo production of the 642 plant-derived alkaloid strictosidine in yeast. Proceedings of the National Academy 643 of Sciences 112: 3205-3210 644

Brückner C, Oreb M, Kunze G, Boles E, Tripp J (2018) An expanded enzyme toolbox 645 for production of cis, cis-muconic acid and other shikimate pathway derivatives in 646 Saccharomyces cerevisiae. FEMS Yeast Research 18: foy017 647

Camesasca L, Minteguiaga M, Fariña L, Salzman V, Aguilar P, Gaggero C, Carrau 648 F (2018) Overproduction of isoprenoids by Saccharomyces cerevisiae in a 649 synthetic grape juice medium in the absence of plant genes. International Journal 650 of Food Microbiology 282: 42-48 651

Campbell A, Bauchart P, Gold ND, Zhu Y, De Luca V, Martin VJ (2016) 652 Engineering of a nepetalactol-producing platform strain of Saccharomyces 653 cerevisiae for the production of plant seco-iridoids. ACS synthetic biology 5: 654 405-414 655

Canelas AB, Harrison N, Fazio A, Zhang J, Pitkänen J-P, Van den Brink J, Bakker 656 BM, Bogner L, Bouwman J, Castrillo JI (2010) Integrated multilaboratory 657 systems biology reveals differences in protein metabolism between two reference 658 yeast strains. Nature Communications 1: 145 659

Caputi L, Franke J, Farrow SC, Chung K, Payne RM, Nguyen T-D, Dang T-TT, 660 Carqueijeiro IST, Koudounas K, de Bernonville TD (2018) Missing enzymes 661 in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. 662 Science 360: 1235-1239 663

Cardenas J, Da Silva NA (2016) Engineering cofactor and transport mechanisms in 664 Saccharomyces cerevisiae for enhanced acetyl-CoA and polyketide biosynthesis. 665 Metabolic Engineering 36: 80-89 666

Casini A, Chang F-Y, Eluere R, King AM, Young EM, Dudley QM, Karim A, Pratt 667 K, Bristol C, Forget A (2018) A pressure test to make 10 molecules in 90 days: 668 External evaluation of methods to engineer biology. Journal of the American 669 Chemical Society 140: 4302-4316 670

Chambon C, Ladeveze V, Oulmouden A, Servouse M, Karst F (1990) Isolation and 671 properties of yeast mutants affected in farnesyl diphosphate synthetase. Current 672 Genetics 18: 41-46 673

Chang MC, Eachus RA, Trieu W, Ro D-K, Keasling JD (2007) Engineering 674 Escherichia coli for production of functionalized terpenoids using plant P450s. 675 Nature Chemical Biology 3: 274 676

Chao R, Mishra S, Si T, Zhao H (2017) Engineering biological systems using 677 automated biofoundries. Metabolic Engineering 42: 98-108 678

Chemler JA, Fowler ZL, McHugh KP, Koffas MA (2010) Improving NADPH 679 availability for natural product biosynthesis in Escherichia coli by metabolic 680 engineering. Metabolic Engineering 12: 96-104 681

Chen X, Yang X, Shen Y, Hou J, Bao X (2017) Increasing malonyl-CoA derived 682 product through controlling the transcription regulators of phospholipid synthesis 683 in Saccharomyces cerevisiae. ACS Synthetic Biology 6: 905-912 684



32

Chen X, Yang X, Shen Y, Hou J, Bao X (2018) Screening phosphorylation site 685 mutations in yeast acetyl-CoA carboxylase using malonyl-CoA sensor to Improve 686 malonyl-CoA-derived product. Frontiers in microbiology 9: 47 687

Chen Y, Xiao W, Wang Y, Liu H, Li X, Yuan Y (2016) Lycopene overproduction in 688 Saccharomyces cerevisiae through combining pathway engineering with host 689 engineering. Microbial Cell Factories 15: 113 690

Choi JW, Da Silva NA (2014) Improving polyketide and fatty acid synthesis by 691 engineering of the yeast acetyl-CoA carboxylase. Journal of Biotechnology 187: 692 56-59 693

Connolly J, Hill R (1991) Dictionary of Terpenes. In. Chapman and Hall 694 Davis MS, Solbiati J, Cronan J (2000) Overproduction of acetyl-CoA carboxylase 695

activity increases the rate of fatty acid biosynthesis in Escherichia coli. Journal of 696 Biological Chemistry 275: 28593-28598 697

DeLoache WC, Russ ZN, Narcross L, Gonzales AM, Martin VJ, Dueber JE (2015) 698 An enzyme-coupled biosensor enables (S)-reticuline production in yeast from 699 glucose. Nature Chemical Biology 11: 465-471 700

Denby CM, Li RA, Vu VT, Costello Z, Lin W, Chan LJG, Williams J, Donaldson B, 701 Bamforth CW, Petzold CJ (2018) Industrial brewing yeast engineered for the 702 production of primary flavor determinants in hopped beer. Nature 703 Communications 9: 965 704

Ding M-z, Yan H-f, Li L-f, Zhai F, Shang L-q, Yin Z, Yuan Y-j (2014) Biosynthesis 705 of Taxadiene in Saccharomyces cerevisiae: selection of geranylgeranyl 706 diphosphate synthase directed by a computer-aided docking strategy. PloS one 9: 707 e109348 708

Duan L, Ding W, Liu X, Cheng X, Cai J, Hua E, Jiang H (2017) Biosynthesis and 709 engineering of kaempferol in Saccharomyces cerevisiae. Microbial Cell Factories 710 16: 165 711

Dudnik A, Almeida AF, Andrade R, Avila B, Bañados P, Barbay D, Bassard J-E, 712 Benkoulouche M, Bott M, Braga A (2018) BacHBerry: BACterial Hosts for 713 production of Bioactive phenolics from bERRY fruits. Phytochemistry Reviews 714 17: 291-326 715

Eichenberger M, Hansson A, Fischer D, Dürr L, Naesby M (2018) De novo 716 biosynthesis of anthocyanins in Saccharomyces cerevisiae. FEMS Yeast Research 717 18: foy046 718

Eichenberger M, Lehka BJ, Folly C, Fischer D, Martens S, Simón E, Naesby M 719 (2017) Metabolic engineering of Saccharomyces cerevisiae for de novo 720 production of dihydrochalcones with known antioxidant, antidiabetic, and sweet 721 tasting properties. Metabolic Engineering 39: 80-89 722

Farrow SC, Hagel JM, Beaudoin GA, Burns DC, Facchini PJ (2015) Stereochemical 723 inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy. Nature 724 Chemical Biology 11: 728-732 725

Fossati E, Ekins A, Narcross L, Zhu Y, Falgueyret J-P, Beaudoin GA, Facchini PJ, 726 Martin VJ (2014) Reconstitution of a 10-gene pathway for synthesis of the plant 727 alkaloid dihydrosanguinarine in Saccharomyces cerevisiae. Nature 728 Communications 5 729



33

Fossati E, Narcross L, Ekins A, Falgueyret J-P, Martin VJ (2015) Synthesis of 730 morphinan alkaloids in Saccharomyces cerevisiae. PloS One 10: e0124459 731

Fowler ZL, Gikandi WW, Koffas MA (2009) Increased malonyl coenzyme A 732 biosynthesis by tuning the Escherichia coli metabolic network and its application 733 to flavanone production. Applied and Environmental Microbiology 75: 5831-734 5839 735

Frick S, Ounaroon A, Kutchan TM (2001) Combinatorial biochemistry in plants: the 736 case of O-methyltransferases. Phytochemistry 56: 1-4 737

Galanie S, Thodey K, Trenchard IJ, Interrante MF, Smolke CD (2015) Complete 738 biosynthesis of opioids in yeast. Science 349: 1095-1100 739

Gao M, Cao M, Suastegui M, Walker J, Rodriguez Quiroz N, Wu Y, Tribby D, 740 Okerlund A, Stanley L, Shanks JV (2016) Innovating a nonconventional yeast 741 platform for producing shikimate as the building block of high-value aromatics. 742 ACS Synthetic Biology 6: 29-38 743

Gaspar P, Carvalho AL, Vinga S, Santos H, Neves AR (2013) From physiology to 744 systems metabolic engineering for the production of biochemicals by lactic acid 745 bacteria. Biotechnology Advances 31: 764-788 746

Geu-Flores F, Sherden NH, Courdavault V, Burlat V, Glenn WS, Wu C, Nims E, 747 Cui Y, O’connor SE (2012) An alternative route to cyclic terpenes by reductive 748 cyclization in iridoid biosynthesis. Nature 492: 138 749

Glenn WS, Runguphan W, O’Connor SE (2013) Recent progress in the metabolic 750 engineering of alkaloids in plant systems. Current Opinion in Biotechnology 24: 751 354-365 752

Gold ND, Gowen CM, Lussier F-X, Cautha SC, Mahadevan R, Martin VJ (2015) 753 Metabolic engineering of a tyrosine-overproducing yeast platform using targeted 754 metabolomics. Microbial cell factories 14: 1 755

Hagel JM, Krizevski R, Marsolais F, Lewinsohn E, Facchini PJ (2012) Biosynthesis 756 of amphetamine analogs in plants. Trends in Plant Science 17: 404-412 757

Hausjell J, Halbwirth H, Spadiut O (2018) Recombinant production of eukaryotic 758 cytochrome P450s in microbial cell factories. Bioscience Reports: BSR20171290 759

Hawkins KM, Smolke CD (2008) Production of benzylisoquinoline alkaloids in 760 Saccharomyces cerevisiae. Nature Chemical Biology 4: 564-573 761

Hazelwood LA, Daran J-M, van Maris AJ, Pronk JT, Dickinson JR (2008) The 762 Ehrlich pathway for fusel alcohol production: a century of research on 763 Saccharomyces cerevisiae metabolism. Applied and Environmental Microbiology 764 74: 2259-2266 765

Heo KT, Kang S-Y, Hong Y-S (2017) De novo biosynthesis of pterostilbene in an 766 Escherichia coli strain using a new resveratrol O-methyltransferase from 767 Arabidopsis. Microbial Cell Factories 16: 30 768

Horwitz AA, Walter JM, Schubert MG, Kung SH, Hawkins K, Platt DM, Hernday 769 AD, Mahatdejkul-Meadows T, Szeto W, Chandran SS (2015) Efficient 770 multiplexed integration of synergistic alleles and metabolic pathways in yeasts via 771 CRISPR-Cas. Cell Systems 772

Ignea C, Cvetkovic I, Loupassaki S, Kefalas P, Johnson CB, Kampranis SC, Makris 773 AM (2011) Improving yeast strains using recyclable integration cassettes, for the 774 production of plant terpenoids. Microbial Cell Factories 10: 4 775



34

Ikeda M, Ozaki A, Katsumata R (1993) Phenylalanine production by metabolically 776 engineered Corynebacterium glutamicum with the pheA gene of Escherichia coli. 777 Applied Microbiology and Biotechnology 39: 318-323 778

Jakočiūnas T, Bonde I, Herrgård M, Harrison SJ, Kristensen M, Pedersen LE, 779 Jensen MK, Keasling JD (2015) Multiplex metabolic pathway engineering using 780 CRISPR/Cas9 in Saccharomyces cerevisiae. Metabolic Engineering 28: 213-222 781

Jakočiūnas T, Jensen MK, Keasling JD (2017) System-level perturbations of cell 782 metabolism using CRISPR/Cas9. Current Opinion in Biotechnology 46: 134-140 783

Jiang G-Z, Yao M-D, Wang Y, Zhou L, Song T-Q, Liu H, Xiao W-H, Yuan Y-J 784 (2017) Manipulation of GES and ERG20 for geraniol overproduction in 785 Saccharomyces cerevisiae. Metabolic Engineering 41: 57-66 786

Jones J, Vernacchio V, Collins S, Shirke A, Xiu Y, Englaender J, Cress B, 787 McCutcheon C, Linhardt R, Gross R (2017) Complete biosynthesis of 788 anthocyanins using E. coli polycultures. 8 789

Jongedijk E, Cankar K, Ranzijn J, Krol S, Bouwmeester H, Beekwilder J (2015) 790 Capturing of the monoterpene olefin limonene produced in Saccharomyces 791 cerevisiae. Yeast 32: 159-171 792

Kai K, Mizutani M, Kawamura N, Yamamoto R, Tamai M, Yamaguchi H, Sakata 793 K, Shimizu Bi (2008) Scopoletin is biosynthesized via ortho-hydroxylation of 794 feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana. 795 The Plant Journal 55: 989-999 796

Kallscheuer N, Classen T, Drepper T, Marienhagen J (2019) Production of plant 797 metabolites with applications in the food industry using engineered 798 microorganisms. Current Opinion in Biotechnology 56: 7-17 799

Kaneko M, Hwang EI, Ohnishi Y, Horinouchi S (2003) Heterologous production of 800 flavanones in Escherichia coli: potential for combinatorial biosynthesis of 801 flavonoids in bacteria. Journal of Industrial Microbiology and Biotechnology 30: 802 456-461 803

Kang S-Y, Lee JK, Choi O, Kim CY, Jang J-H, Hwang BY, Hong Y-S (2014) 804 Biosynthesis of methylated resveratrol analogs through the construction of an 805 artificial biosynthetic pathway in E. coli. BMC Biotechnology 14: 67 806

Katz M, Forster J, David H, Schmidt HP, Sendelius M, Bjorn SP, Durhuus TT 807 (2017) Metabolically engineered cells for the production of pinosylvin. In. Google 808 Patents 809

Katz MP, Durhuus T, Smits HP, Förster J (2017) Production of metabolites. In. 810 Google Patents 811

King JR, Woolston BM, Stephanopoulos G (2017) Designing a new entry point into 812 isoprenoid metabolism by exploiting fructose-6-phosphate aldolase side reactivity 813 of Escherichia coli. ACS Synthetic Biology 6: 1416-1426 814

Kita T, Imai S, Sawada H, Kumagai H, Seto H (2008) The biosynthetic pathway of 815 curcuminoid in turmeric (Curcuma longa) as revealed by

13C-labeled precursors. 816

Bioscience, Biotechnology, and Biochemistry 72: 1789-1798 817 Kozak BU, van Rossum HM, Benjamin KR, Wu L, Daran J-MG, Pronk JT, van 818

Maris AJ (2014) Replacement of the Saccharomyces cerevisiae acetyl-CoA 819 synthetases by alternative pathways for cytosolic acetyl-CoA synthesis. Metabolic 820 Engineering 21: 46-59 821



35

Kozak BU, van Rossum HM, Luttik MA, Akeroyd M, Benjamin KR, Wu L, de 822 Vries S, Daran J-M, Pronk JT, van Maris AJ (2014) Engineering acetyl 823 coenzyme A supply: functional expression of a bacterial pyruvate dehydrogenase 824 complex in the cytosol of Saccharomyces cerevisiae. MBio 5: e01696-01614 825

Kozak BU, van Rossum HM, Niemeijer MS, van Dijk M, Benjamin K, Wu L, Daran 826 J-MG, Pronk JT, van Maris AJ (2016) Replacement of the initial steps of 827 ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating 828 acetaldehyde dehydrogenase. FEMS Yeast Research 16 829

Lange BM, Ahkami A (2013) Metabolic engineering of plant monoterpenes, 830 sesquiterpenes and diterpenes—current status and future opportunities. Plant 831 Biotechnology Journal 11: 169-196 832

Lee ME, DeLoache WC, Cervantes B, Dueber JE (2015) A highly characterized yeast 833 toolkit for modular, multipart assembly. ACS Synthetic Biology 4: 975-986 834

Lehka BJ, Eichenberger M, Bjørn-Yoshimoto WE, Vanegas KG, Buijs N, Jensen 835 NB, Dyekjær JD, Jenssen H, Simon E, Naesby M (2016) Improving 836 heterologous production of phenylpropanoids in Saccharomyces cerevisiae by 837 tackling an unwanted side reaction of Tsc13, an endogenous double-bond 838 reductase. FEMS Yeast Research 17: fox004 839

Leonard E, Lim K-H, Saw P-N, Koffas MA (2007) Engineering central metabolic 840 pathways for high-level flavonoid production in Escherichia coli. Applied and 841 Environmental Microbiology 73: 3877-3886 842

Leonard E, Yan Y, Fowler ZL, Li Z, Lim C-G, Lim K-H, Koffas MA (2008) Strain 843 improvement of recombinant Escherichia coli for efficient production of plant 844 flavonoids. Molecular Pharmaceutics 5: 257-265 845

Levisson M, Patinios C, Hein S, de Groot PA, Daran J-M, Hall RD, Martens S, 846 Beekwilder J (2018) Engineering de novo anthocyanin production in 847 Saccharomyces cerevisiae. Microbial Cell Factories 17: 103 848

Li C, Ying L-Q, Zhang S-S, Chen N, Liu W-F, Tao Y (2015) Modification of targets 849 related to the Entner–Doudoroff/pentose phosphate pathway route for methyl-d-850 erythritol 4-phosphate-dependent carotenoid biosynthesis in Escherichia coli. 851 Microbial Cell Factories 14: 117 852

Li J, Lee E-J, Chang L, Facchini PJ (2016) Genes encoding norcoclaurine synthase 853 occur as tandem fusions in the Papaveraceae. Scientific Reports 6: 39256 854

Li M, Schneider K, Kristensen M, Borodina I, Nielsen J (2016) Engineering yeast for 855 high-level production of stilbenoid antioxidants. Scientific Reports 6: 36827 856

Li Y, Li S, Thodey K, Trenchard I, Cravens A, Smolke CD (2018) Complete 857 biosynthesis of noscapine and halogenated alkaloids in yeast. Proceedings of the 858 National Academy of Sciences 115: E3922-E3931 859

Lian J, HamediRad M, Hu S, Zhao H (2017) Combinatorial metabolic engineering 860 using an orthogonal tri-functional CRISPR system. Nature Communications 8: 861 1688 862

Liang J-l, Guo L-q, Lin J-f, He Z-q, Cai F-j, Chen J-f (2016) A novel process for 863 obtaining pinosylvin using combinatorial bioengineering in Escherichia coli. 864 World Journal of Microbiology and Biotechnology 32: 102 865



36

Lichman BR, Zhao J, Hailes HC, Ward JM (2017) Enzyme catalysed Pictet-Spengler 866 formation of chiral 1, 1’-disubstituted-and spiro-tetrahydroisoquinolines. Nature 867 Communications 8: 14883 868

Lin Y, Shen X, Yuan Q, Yan Y (2013) Microbial biosynthesis of the anticoagulant 869 precursor 4-hydroxycoumarin. Nature Communications 4: 2603 870

Liu M, Ding Y, Chen H, Zhao Z, Liu H, Xian M, Zhao G (2017) Improving the 871 production of acetyl-CoA-derived chemicals in Escherichia coli BL21 (DE3) 872 through iclR and arcA deletion. BMC Microbiology 17: 10 873

Liu W, Xu X, Zhang R, Cheng T, Cao Y, Li X, Guo J, Liu H, Xian M (2016) 874 Engineering Escherichia coli for high-yield geraniol production with 875 biotransformation of geranyl acetate to geraniol under fed-batch culture. 876 Biotechnology for biofuels 9: 58 877

Liu W, Zhang B, Jiang R (2017) Improving acetyl-CoA biosynthesis in Saccharomyces 878 cerevisiae via the overexpression of pantothenate kinase and PDH bypass. 879 Biotechnology for biofuels 10: 41 880

Liu X, Cheng J, Zhang G, Ding W, Duan L, Yang J, Kui L, Cheng X, Ruan J, Fan 881 W (2018) Engineering yeast for the production of breviscapine by genomic 882 analysis and synthetic biology approaches. Nature Communications 9: 448 883

Lussier F-X, Colatriano D, Wiltshire Z, Page JE, Martin VJ (2012) Engineering 884 microbes for plant polyketide biosynthesis. Computational and structural 885 biotechnology journal 3: e201210020 886

Luttik M, Vuralhan Z, Suir E, Braus G, Pronk J, Daran J (2008) Alleviation of 887 feedback inhibition in Saccharomyces cerevisiae aromatic amino acid 888 biosynthesis: quantification of metabolic impact. Metabolic engineering 10: 141-889 153 890

Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003) Engineering a 891 mevalonate pathway in Escherichia coli for production of terpenoids. Nature 892 biotechnology 21: 796-802 893

Matasci N, Hung L-H, Yan Z, Carpenter EJ, Wickett NJ, Mirarab S, Nguyen N, 894 Warnow T, Ayyampalayam S, Barker M (2014) Data access for the 1,000 895 Plants (1KP) project. GigaScience 3: 1-10 896

Matsumura E, Nakagawa A, Tomabechi Y, Ikushiro S, Sakaki T, Katayama T, 897 Yamamoto K, Kumagai H, Sato F, Minami H (2018) Microbial production of 898 novel sulphated alkaloids for drug discovery. Scientific Reports 8: 7980 899

Meadows AL, Hawkins KM, Tsegaye Y, Antipov E, Kim Y, Raetz L, Dahl RH, Tai 900 A, Mahatdejkul-Meadows T, Xu L (2016) Rewriting yeast central carbon 901 metabolism for industrial isoprenoid production. Nature 537: 694-697 902

Mendez‐Perez D, Alonso‐Gutierrez J, Hu Q, Molinas M, Baidoo EE, Wang G, 903 Chan LJ, Adams PD, Petzold CJ, Keasling JD (2017) Production of jet fuel 904 precursor monoterpenoids from engineered Escherichia coli. Biotechnology and 905 Bioengineering 114: 1703-1712 906

Meunier B, de Visser SP, Shaik S (2004) Mechanism of oxidation reactions catalyzed 907 by cytochrome P450 enzymes. Chemical Reviews 104: 3947-3980 908

Miettinen K, Dong L, Navrot N, Schneider T, Burlat V, Pollier J, Woittiez L, van 909 der Krol S, Lugan R, Ilc T (2014) The seco-iridoid pathway from Catharanthus 910 roseus. Nature communications 5 911



37

Morris JS, Groves RA, Hagel JM, Facchini PJ (2018) An N-methyltransferase from 912 Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine 913 enables microbial phenylalkylamine production. Journal of Biological Chemistry: 914 jbc. RA118. 004067 915

Munro AW, Leys DG, McLean KJ, Marshall KR, Ost TW, Daff S, Miles CS, 916 Chapman SK, Lysek DA, Moser CC (2002) P450 BM3: the very model of a 917 modern flavocytochrome. Trends in Biochemical Sciences 27: 250-257 918

Nakagawa A, Matsumura E, Koyanagi T, Katayama T, Kawano N, Yoshimatsu K, 919 Yamamoto K, Kumagai H, Sato F, Minami H (2016) Total biosynthesis of 920 opiates by stepwise fermentation using engineered Escherichia coli. Nature 921 communications 7 922

Nakagawa A, Matsuzaki C, Matsumura E, Koyanagi T, Katayama T, Yamamoto K, 923 Sato F, Kumagai H, Minami H (2014) (R, S)-tetrahydropapaveroline production 924 by stepwise fermentation using engineered Escherichia coli. Scientific reports 4: 925 6695 926

Nakagawa A, Minami H, Kim J-S, Koyanagi T, Katayama T, Sato F, Kumagai H 927 (2011) A bacterial platform for fermentative production of plant alkaloids. Nature 928 Communications 2: 326 929

Narcross L, Bourgeois L, Fossati E, Burton E, Martin VJ (2016) Mining enzyme 930 diversity of transcriptome libraries through DNA synthesis for benzylisoquinoline 931 alkaloid pathway optimization in yeast. ACS synthetic biology 5: 1505-1518 932

Narcross L, Fossati E, Bourgeois L, Dueber JE, Martin VJ (2016) Microbial factories 933 for the production of benzylisoquinoline alkaloids. Trends in biotechnology 34: 934 228-241 935

Nielsen J, Keasling JD (2016) Engineering cellular metabolism. Cell 164: 1185-1197 936 Nishihachijo M, Hirai Y, Kawano S, Nishiyama A, Minami H, Katayama T, 937

Yasohara Y, Sato F, Kumagai H (2014) Asymmetric synthesis of 938 tetrahydroisoquinolines by enzymatic Pictet–Spengler reaction. Bioscience, 939 Biotechnology, and Biochemistry 78: 701-707 940

Ounaroon A, Decker G, Schmidt J, Lottspeich F, Kutchan TM (2003) (R, S)-941 Reticuline 7-O-methyltransferase and (R, S)-norcoclaurine 6-O-methyltransferase 942 of Papaver somniferum–cDNA cloning and characterization of methyl transfer 943 enzymes of alkaloid biosynthesis in opium poppy. The Plant Journal 36: 808-819 944

Ozaydın B, Burd H, Lee TS, Keasling JD (2013) Carotenoid-based phenotypic screen 945 of the yeast deletion collection reveals new genes with roles in isoprenoid 946 production. Metabolic Engineering 15: 174-183 947

Paddon CJ, Westfall PJ, Pitera D, Benjamin K, Fisher K, McPhee D, Leavell M, Tai 948 A, Main A, Eng D (2013) High-level semi-synthetic production of the potent 949 antimalarial artemisinin. Nature 496: 528-532 950

Patnaik R, Zolandz RR, Green DA, Kraynie DF (2008) L-Tyrosine production by 951 recombinant Escherichia coli: Fermentation optimization and recovery. 952 Biotechnology and bioengineering 99: 741-752 953

Peralta-Yahya PP, Ouellet M, Chan R, Mukhopadhyay A, Keasling JD, Lee TS 954 (2011) Identification and microbial production of a terpene-based advanced 955 biofuel. Nature Communications 2: 483 956



38

Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating 957 signal peptides from transmembrane regions. Nature Methods 8: 785 958

Porter TD (2002) The roles of cytochrome b5 in cytochrome P450 reactions. Journal of 959 Biochemical and Molecular Toxicology 16: 311-316 960

Preisig-Müller R, Schwekendiek A, Brehm I, Reif H-J, Kindl H (1999) 961 Characterization of a pine multigene family containing elicitor-responsive stilbene 962 synthase genes. Plant Molecular Biology 39: 221-229 963

Qu Y, Easson ML, Froese J, Simionescu R, Hudlicky T, De Luca V (2015) 964 Completion of the seven-step pathway from tabersonine to the anticancer drug 965 precursor vindoline and its assembly in yeast. Proceedings of the National 966 Academy of Sciences 112: 6224-6229 967

Reider Apel A, d'Espaux L, Wehrs M, Sachs D, Li RA, Tong GJ, Garber M, Nnadi 968 O, Zhuang W, Hillson NJ (2016) A Cas9-based toolkit to program gene 969 expression in Saccharomyces cerevisiae. Nucleic Acids Research 45: 496-508 970

Rodriguez A, Kildegaard KR, Li M, Borodina I, Nielsen J (2015) Establishment of a 971 yeast platform strain for production of p-coumaric acid through metabolic 972 engineering of aromatic amino acid biosynthesis. Metabolic Engineering 31: 181-973 188 974

Rodriguez A, Strucko T, Stahlhut SG, Kristensen M, Svenssen DK, Forster J, 975 Nielsen J, Borodina I (2017) Metabolic engineering of yeast for fermentative 976 production of flavonoids. Bioresource Technology 245: 1645-1654 977

Rodriguez S, Denby CM, Vu Tv, Baidoo EE, Wang G, Keasling JD (2016) ATP 978 citrate lyase mediated cytosolic acetyl-CoA biosynthesis increases mevalonate 979 production in Saccharomyces cerevisiae. Microbial cell factories 15: 1 980

Ryan OW, Skerker JM, Maurer MJ, Li X, Tsai JC, Poddar S, Lee ME, DeLoache 981 W, Dueber JE, Arkin AP (2014) Selection of chromosomal DNA libraries using 982 a multiplex CRISPR system. Elife 3: e03703 983

Saunders LP, Bowman MJ, Mertens JA, Da Silva NA, Hector RE (2015) Triacetic 984 acid lactone production in industrial Saccharomyces yeast strains. Journal of 985 Industrial Microbiology & Biotechnology 42: 711-721 986

Schadeweg V, Boles E (2016) n-Butanol production in Saccharomyces cerevisiae is 987 limited by the availability of coenzyme A and cytosolic acetyl-CoA. 988 Biotechnology for biofuels 9: 44 989

Shi S, Chen Y, Siewers V, Nielsen J (2014) Improving production of malonyl coenzyme 990 A-derived metabolites by abolishing Snf1-dependent regulation of Acc1. MBio 5: 991 e01130-01114 992

Strijbis K, Distel B (2010) Intracellular acetyl unit transport in fungal carbon 993 metabolism. Eukaryotic Cell 9: 1809-1815 994

Strucko T, Magdenoska O, Mortensen UH (2015) Benchmarking two commonly used 995 Saccharomyces cerevisiae strains for heterologous vanillin-β-glucoside 996 production. Metabolic Engineering Communications 2: 99-108 997

Sun T, Miao L, Li Q, Dai G, Lu F, Liu T, Zhang X, Ma Y (2014) Production of 998 lycopene by metabolically-engineered Escherichia coli. Biotechnology Letters 999 36: 1515-1522 1000

Takemura M, Tanaka R, Misawa N (2017) Pathway engineering for the production of 1001 β-amyrin and cycloartenol in Escherichia coli—a method to biosynthesize plant-1002



39

derived triterpene skeletons in E. coli. Applied Microbiology and Biotechnology 1003 101: 6615-6625 1004

Tatsis EC, O’Connor SE (2016) New developments in engineering plant metabolic 1005 pathways. Current Opinion in Biotechnology 42: 126-132 1006

Tippmann S, Scalcinati G, Siewers V, Nielsen J (2016) Production of farnesene and 1007 santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-1008 controlled feed. Biotechnology and Bioengineering 113: 72-81 1009

Trantas E, Panopoulos N, Ververidis F (2009) Metabolic engineering of the complete 1010 pathway leading to heterologous biosynthesis of various flavonoids and 1011 stilbenoids in Saccharomyces cerevisiae. Metabolic Engineering 11: 355-366 1012

Tsuruta H, Paddon CJ, Eng D, Lenihan JR, Horning T, Anthony LC, Regentin R, 1013 Keasling JD, Renninger NS, Newman JD (2009) High-level production of 1014 amorpha-4, 11-diene, a precursor of the antimalarial agent artemisinin, in 1015 Escherichia coli. PLoS One 4: e4489 1016

van Rossum HM, Kozak BU, Pronk JT, van Maris AJ (2016) Engineering cytosolic 1017 acetyl-coenzyme A supply in Saccharomyces cerevisiae: pathway stoichiometry, 1018 free-energy conservation and redox-cofactor balancing. Metabolic Engineering 1019 36: 99-115 1020

Vickery CR, La Clair JJ, Burkart MD, Noel JP (2016) Harvesting the biosynthetic 1021 machineries that cultivate a variety of indispensable plant natural products. 1022 Current Opinion in Chemical Biology 31: 66-73 1023

Vogt T (2010) Phenylpropanoid biosynthesis. Molecular plant 3: 2-20 1024 Wang Q, Xu J, Sun Z, Luan Y, Li Y, Wang J, Liang Q, Qi Q (2018) Engineering an 1025

in vivo EP-bifido pathway in Escherichia coli for high-yield acetyl-CoA 1026 generation with low CO2 emission. Metabolic Engineering (in press) 1027

Wang R-z, Pan C-h, Wang Y, Xiao W-h, Yuan Y-j (2016) Design and construction of 1028 high β-carotene producing Saccharomyces cerevisiae. China Biotechnology 36: 1029 83-91 1030

Wang S, Zhang S, Xiao A, Rasmussen M, Skidmore C, Zhan J (2015) Metabolic 1031 engineering of Escherichia coli for the biosynthesis of various phenylpropanoid 1032 derivatives. Metabolic Engineering 29: 153-159 1033

Watts KT, Lee PC, Schmidt-Dannert C (2006) Biosynthesis of plant-specific stilbene 1034 polyketides in metabolically engineered Escherichia coli. BMC Biotechnology 6: 1035 22 1036

Westfall PJ, Pitera DJ, Lenihan JR, Eng D, Woolard FX, Regentin R, Horning T, 1037 Tsuruta H, Melis DJ, Owens A (2012) Production of amorphadiene in yeast, and 1038 its conversion to dihydroartemisinic acid, precursor to the antimalarial agent 1039 artemisinin. Proceedings of the National Academy of Sciences 109: E111-E118 1040

Williams DC, McGarvey DJ, Katahira EJ, Croteau R (1998) Truncation of limonene 1041 synthase preprotein provides a fully active ‘pseudomature'form of this 1042 monoterpene cyclase and reveals the function of the amino-terminal arginine pair. 1043 Biochemistry 37: 12213-12220 1044

Willrodt C, David C, Cornelissen S, Bühler B, Julsing MK, Schmid A (2014) 1045 Engineering the productivity of recombinant Escherichia coli for limonene 1046 formation from glycerol in minimal media. Biotechnology journal 9: 1000-1012 1047



40

Wilson SA, Roberts SC (2014) Metabolic engineering approaches for production of 1048 biochemicals in food and medicinal plants. Current Opinion in Biotechnology 26: 1049 174-182 1050

Winzer T, Kern M, King AJ, Larson TR, Teodor RI, Donninger SL, Li Y, Dowle 1051 AA, Cartwright J, Bates R (2015) Morphinan biosynthesis in opium poppy 1052 requires a P450-oxidoreductase fusion protein. Science 349: 309-312 1053

Wong J, de Rond T, d’Espaux L, van der Horst C, Dev I, Rios-Solis L, Kirby J, 1054 Scheller H, Keasling J (2018) High-titer production of lathyrane diterpenoids 1055 from sugar by engineered Saccharomyces cerevisiae. Metabolic Engineering 45: 1056 142-148 1057

Wriessnegger T, Augustin P, Engleder M, Leitner E, Müller M, Kaluzna I, 1058 Schürmann M, Mink D, Zellnig G, Schwab H (2014) Production of the 1059 sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris. 1060 Metabolic Engineering 24: 18-29 1061

Wu J, Zhang X, Dong M, Zhou J (2016) Stepwise modular pathway engineering of 1062 Escherichia coli for efficient one-step production of (2S)-pinocembrin. Journal of 1063 Biotechnology 231: 183-192 1064

Wu J, Zhang X, Zhou J, Dong M (2016) Efficient biosynthesis of (2S)-pinocembrin 1065 from D-glucose by integrating engineering central metabolic pathways with a pH-1066 shift control strategy. Bioresource Technology 218: 999-1007 1067

Wu J, Zhang X, Zhu Y, Tan Q, He J, Dong M (2017) Rational modular design of 1068 metabolic network for efficient production of plant polyphenol pinosylvin. 1069 Scientific Reports 7: 1459 1070

Wu S, Chappell J (2008) Metabolic engineering of natural products in plants; tools of 1071 the trade and challenges for the future. Current Opinion in Biotechnology 19: 1072 145-152 1073

Xiao M, Zhang Y, Chen X, Lee E-J, Barber CJ, Chakrabarty R, Desgagné-Penix I, 1074 Haslam TM, Kim Y-B, Liu E (2013) Transcriptome analysis based on next-1075 generation sequencing of non-model plants producing specialized metabolites of 1076 biotechnological interest. Journal of Biotechnology 166: 122-134 1077

Xu P, Ranganathan S, Fowler ZL, Maranas CD, Koffas MA (2011) Genome-scale 1078 metabolic network modeling results in minimal interventions that cooperatively 1079 force carbon flux towards malonyl-CoA. Metabolic Engineering 13: 578-587 1080

Yamanishi M, Ito Y, Kintaka R, Imamura C, Katahira S, Ikeuchi A, Moriya H, 1081 Matsuyama T (2013) A genome-wide activity assessment of terminator regions 1082 in Saccharomyces cerevisiae provides a ″terminatome″ toolbox. ACS Synthetic 1083 Biology 2: 337-347 1084

Yan Y, Kohli A, Koffas MA (2005) Biosynthesis of natural flavanones in 1085 Saccharomyces cerevisiae. Applied and Environmental Microbiology 71: 5610-1086 5613 1087

Yang D, Kim WJ, Yoo SM, Choi JH, Ha SH, Lee MH, Lee SY (2018) Repurposing 1088 type III polyketide synthase as a malonyl-CoA biosensor for metabolic 1089 engineering in bacteria. Proceedings of the National Academy of Sciences: 1090 201808567 1091

Yang J, Guo L (2014) Biosynthesis of β-carotene in engineered E. coli using the MEP 1092 and MVA pathways. Microbial Cell Factories 13: 160 1093



41

Yang J, Li Z, Guo L, Du J, Bae H-J (2016) Biosynthesis of β-caryophyllene, a novel 1094 terpene-based high-density biofuel precursor, using engineered Escherichia coli. 1095 Renewable Energy 99: 216-223 1096

Yang J, Nie Q, Ren M, Feng H, Jiang X, Zheng Y, Liu M, Zhang H, Xian M (2013) 1097 Metabolic engineering of Escherichia coli for the biosynthesis of alpha-pinene. 1098 Biotechnology for biofuels 6: 60 1099

Yang S-M, Han SH, Kim B-G, Ahn J-H (2014) Production of kaempferol 3-O-1100 rhamnoside from glucose using engineered Escherichia coli. Journal of Industrial 1101 Microbiology & Biotechnology 41: 1311-1318 1102

Yang S-M, Shim GY, Kim B-G, Ahn J-H (2015) Biological synthesis of coumarins in 1103 Escherichia coli. Microbial Cell Factories 14: 65 1104

Yang Y, Lin Y, Li L, Linhardt RJ, Yan Y (2015) Regulating malonyl-CoA metabolism 1105 via synthetic antisense RNAs for enhanced biosynthesis of natural products. 1106 Metabolic Engineering 29: 217-226 1107

Yao R, Zhao Y, Liu T, Huang C, Xu S, Sui Z, Luo J, Kong L (2017) Identification 1108 and functional characterization of a p-coumaroyl CoA 2′-hydroxylase involved 1109 in the biosynthesis of coumarin skeleton from Peucedanum praeruptorum Dunn. 1110 Plant Molecular Biology 95: 199-213 1111

You S, Yin Q, Zhang J, Zhang C, Qi W, Gao L, Tao Z, Su R, He Z (2017) Utilization 1112 of biodiesel by-product as substrate for high-production of β-farnesene via 1113 relatively balanced mevalonate pathway in Escherichia coli. Bioresource 1114 Technology 243: 228-236 1115

Yu D, Xu F, Zeng J, Zhan J (2012) Type III polyketide synthases in natural product 1116 biosynthesis. IUBMB life 64: 285-295 1117

Zha W, Rubin-Pitel SB, Shao Z, Zhao H (2009) Improving cellular malonyl-CoA level 1118 in Escherichia coli via metabolic engineering. Metabolic Engineering 11: 192-1119 198 1120

Zhang C, Chen X, Lindley ND, Too HP (2018) A “plug‐n‐play” modular 1121 metabolic system for the production of apocarotenoids. Biotechnology and 1122 Bioengineering 115: 174-183 1123

Zhang C, Liu J, Zhao F, Lu C, Zhao G-R, Lu W (2018) Production of sesquiterpenoid 1124 zerumbone from metabolic engineered Saccharomyces cerevisiae. Metabolic 1125 Engineering 49: 28-35 1126

Zhang Y, Dai Z, Krivoruchko A, Chen Y, Siewers V, Nielsen J (2015) Functional 1127 pyruvate formate lyase pathway expressed with two different electron donors in 1128 Saccharomyces cerevisiae at aerobic growth. FEMS Yeast Research 15 1129

Zhang Y, Li S-Z, Li J, Pan X, Cahoon RE, Jaworski JG, Wang X, Jez JM, Chen F, 1130 Yu O (2006) Using unnatural protein fusions to engineer resveratrol biosynthesis 1131 in yeast and mammalian cells. Journal of the American Chemical Society 128: 1132 13030-13031 1133

Zhao J, Bao X, Li C, Shen Y, Hou J (2016) Improving monoterpene geraniol 1134 production through geranyl diphosphate synthesis regulation in Saccharomyces 1135 cerevisiae. Applied Microbiology and Biotechnology 100: 4561-4571 1136

Zhao Y, Liu T, Luo J, Zhang Q, Xu S, Han C, Xu J, Chen M, Chen Y, Kong L 1137 (2015) Integration of a decrescent transcriptome and metabolomics dataset of 1138



42

Peucedanum praeruptorum to investigate the CYP450 and MDR genes involved 1139 in coumarins biosynthesis and transport. Frontiers in plant science 6: 996 1140

Zhou K, Qiao K, Edgar S, Stephanopoulos G (2015) Distributing a metabolic pathway 1141 among a microbial consortium enhances production of natural products. Nature 1142 Biotechnology 33: 377-383 1143

Zhou ML, Shao JR, Tang YX (2009) Production and metabolic engineering of 1144 terpenoid indole alkaloids in cell cultures of the medicinal plant Catharanthus 1145 roseus (L.) G. Don (Madagascar periwinkle). Biotechnology and Applied 1146 Biochemistry 52: 313-323 1147

Zhu M, Wang C, Sun W, Zhou A, Wang Y, Zhang G, Zhou X, Huo Y, Li C (2018) 1148 Boosting 11-oxo-β-amyrin and glycyrrhetinic acid synthesis in Saccharomyces 1149 cerevisiae via pairing novel oxidation and reduction system from legume plants. 1150 Metabolic Engineering 45: 43-50 1151

1152 1153



ADVANCES

• Microbial synthesis of plant secondary metabolites is in the midst of a renaissance.

• The elucidation of major plant biosynthetic routes has stimulated the production of high-value natural products in microbial systems.

• Efforts are expanding beyond precursors and branch point intermediates to functionalized end products.

• Although baker’s yeast (Saccharomyces cerevisiae) remains the host of choice for reconstructing plant secondary pathways, the range of alternative hosts has diversified.

• Synthetic biology has enabled the expansion of the plant secondary metabolic space in microbial species.



OUTSTANDING QUESTIONS

• Can microbial production of plant metabolites compete with traditional methods of chemical synthesis and crop-based manufacturing?

• Pathways for several untapped sub-classes of plant specialized metabolites have been elucidated recently (e.g., modified amphetamines and vinblastine). Can these pathways be reconstituted in a microbial species?

• Other functionalized metabolites of immense pharmaceutical value (e.g., paclitaxel) have proven inaccessible to date. What are the limitations and how can they be overcome to realize the microbial synthesis of these important drugs?

• To what extent will emerging synthetic biology workflows reduce the time and cost of advancing bioprocesses from proof-of-concept to large-scale production?

• Will microbial systems provide a viable avenue for drug discovery through the exploitation of enzyme promiscuity and combinatorial biochemistry?



BOX 1. Metabolites of mixed biosynthetic

origin

A number of important plant natural products are derived from mixed biosynthetic origins, obscuring the boundaries between secondary metabolite classes (Box 1 Figure). Within the alkaloid class, MIAs arise through condensation of the tryptophan analog tryptamine and a secoiridoid monoterpene (secologanin). Secologanin can also condense with dopamine, giving rise to emetine and cephaeline, the active alkaloids of the emetic drug ipecac. Nicotine is formed through coupling of two heterocyclic rings of distinct biosynthetic origin. Whereas the pyrrolidine ring derives from ornithine via the tropane alkaloid pathway (Figure 1), the pyridine ring is formed from niacin, itself synthesized from aspartate. Several other alkaloids are formed from products of the phenylpropanoid pathway, such as substituted amphetamines through condensation of pyruvate and benzoic acid, a C6-C1 analog of cinnamic acid (Hagel et al., 2012). Modified amphetamines are also called phenylpropylamino alkaloids to reflect their dual biosynthetic origin. Similarly, the autumnaline scaffold of the phenethylisoquinoline alkaloids is derived through condensation of dopamine and 4-hydroxydihydrocinnamaldehyde, another cinnamic acid derivative. The capsaicinoids produced by chili peppers have a unique tripartite classification, as they are exocyclic alkaloids that arise in part from the phenylpropanoid pathway and polyketide synthesis.

Specifically, coupling of ferulic-acid-derived vanillylamine and a fatty acyl-CoA (8-methyl-6-nonenoyl CoA) derived from valine or leucine gives rise to the capsaicin scaffold. Many other functionalized phenylpropanoids, notably the flavonoids and stilbenoids, are also polyketides involving chain elongation by malonyl-CoA (Figure 3). The curcuminoids and gingerols, responsible for the color and pungency of turmeric and ginger, respectively, are two additional subclasses comprising phenylpropanoid CoA esters linked by a polyketide synthase. Aromatic plant secondary metabolites are also frequently prenylated, which requires a terpenoid donor (Vickery et al., 2016). One such class of natural products is the cannabinoids, of which more than 100 distinct compounds are produced by the cannabis plant (Ahmed et al., 2015). A polyketide synthase catalyzes the decarboxylative condensation of hexanoyl-CoA with three molar equivalents of malonyl-CoA to generate olivetolic acid, which is then prenylated by GPP, generating cannabigerolic acid (CBGA). CBGA is the precursor to tetrahydrocannabinol (THC), cannabidiol, and their derivatives. These bioactive natural products have the potential to treat various medical conditions, including cancer, anorexia, epilepsy, and Alzheimer’s and Huntington’s diseases (Aizpurua-Olaizola et al., 2016).





BOX 2. E. coli versus S. cerevisiae

Most microbial synthesis projects start with the question: E. coli or S. cerevisiae? Yeast alcohol production exemplifies the most ancient industrial bioprocess and both hosts have been exploited extensively in industrial biotechnology. Although many plant CYPs and CPRs can be functionally expressed in bacteria, often following extensive engineering of N-terminal membrane domains, CYPs are typically functional in yeast without modification. Because yeast produces only three native CYPs, interference from heterologous CYP and CPR proteins is generally not problematic. Therefore, we surmise that yeast is the superior host to support the biosynthesis of highly functionalized plant secondary metabolites, particularly those arising from multi-CYP pathways. The occurrence of eight CYP-catalyzed reactions in the downstream taxane pathway precludes the use of bacterial systems for producing these important products. E. coli has been engineered to synthesize the highly functionalized morphinan BIA hydrocodone (Nakagawa et al., 2016), yet the full de novo pathway was split between four engineered strains. The same pathway has been reconstructed within a single S. cerevisiae strain

(Galanie et al., 2015), albeit at lower titers, again highlighting the potential advantages of eukaryotic hosts for synthesizing complex plant secondary metabolites. Analogously, de novo anthocyanin synthesis in E. coli employed four engineered strains (Jones et al., 2017), which again contrasts strategies using S. cerevisiae in which a single strain hosts the full anthocyanin pathway (Eichenberger et al., 2018; Levisson et al., 2018). Although yeast is clearly favored for harboring downstream pathways, precursor titers are often higher in E. coli (e.g., for production of tyrosine, p-coumaric acid, dopamine, reticuline, and taxadiene; Table 1). For instance, E. coli has been engineered to produce 1 g/L of taxadiene (Ajikumar et al., 2010), which contrasts yeast titers of only 72.8 mg/L (Ding et al., 2014). This disparity in precursor production and downstream functionalization points to co-culture strategies in which natural product pathways are divided between E. coli and S. cerevisiae hosts. This approach proved highly effective for the synthesis of functionalized taxanes, in which the taxadiene precursor was secreted by E. coli and imported and derivatized by S. cerevisiae harboring multiple CYP enzymes (Zhou et al., 2015).



Figure 1. Interfacing plant terpenoid secondary metabolic pathways with microbial

metabolism. Plant secondary metabolic reactions and pathways (green) are shown linked to core

microbial metabolism (beige shading; black font). S. cerevisiae is shown as prospective host

species. Key yeast enzymes discussed in the main text are shown. Abbreviations: Bts1,

geranylgeranyl diphosphate synthase; DMAPP, dimethylallyl pyrophosphate; Erg9, squalene

synthase; Erg20, farnesyl pyrophosphate synthetase; FPP, farnesyl pyrophosphate; GPP, geranyl

pyrophosphate; GGPP, geranylgeranyl pyrophosphate; IPP, isopentenyl pyrophosphate; MEV,

mevalonate pathway.

Sugars

Pyruvate

Acetyl-CoA

IPP

MONO-

TERPENOIDS

SESQUI-

TERPENOIDS

DI-

TERPENOIDS

GPPGeraniol

Taxadiene

Squalene

TETRA-TERPENOIDS

FPP

GGPP

Phytoene

Citronellol

OH

OH

β-carotene

TRI-TERPENOIDS

α-Pinene

HH

OH

Menthol

Isoprene Prenol

HEMI-

TERPENOIDS

Lycopene

Bisabolene

POLY-

TERPENOIDS

IPP

Farnesol

Erg20

Amorphadiene Artemisinic acid

Limonene

FerruginolGGPP

Natural rubber

(polyisoprene)

n IPP

n IPP

β-Amyrin Lupeol

Erg20

Erg9

Bts1

Ergosterol

Farnesene

OH

OH

OH

O

Camphor

OH

Thymol

OH

Linalool

OH

n>5,000

DMAPP

FPP

OH

MEV

IPP

OH

O



Figure 2. Interfacing plant alkaloid secondary metabolic pathways with microbial metabolism. S. cerevisiae is shown as

prospective host species. Refer to Figure 1 for abbreviations and color coding. Additional abbreviations: AAA path, aromatic amino

acid pathway; Aro1, pentafunctional arom protein; Aro2, chorismate synthase and Flavin reductase; Aro3+Aro4, DAHP synthase

isoenzymes; Aro7, chorismate mutase; E4P, erythrose 4-phosphate; 4-HPAA, 4-hydroxyphenylacetaldehyde; R5P, ribose 5-

phosphate; PPP, pentose phosphate pathway; PEP, phosphoenolpyruvate; TCA cycle, tricarboxylic acid cycle.

Sugars

PEP

Pyruvate

Acetyl-CoA

G6P

R5P

PPP Glycolysis

NucleosidesPURINE ALKALOIDS

Caffeine

BENZYLISOQUINOLINE

ALKALOIDS

MONOTERPENOID INDOLE

ALKALOIDS

Noscapine Morphine Berberine Sanguinarine

TROPANE, PYRROLIDINE, PYRROLIZIDINE,

PYRIDINE ALKALOIDS

PIPERIDINE, QUINOLIZIDINE ALKALOIDS

E4P

Chorismate

Vasicine

QUINAZOLINE

ALKALOIDS

Anthranilate

Prephenate

Nicotine Cocaine Atropine

GPPTryptophan

AMPHETAMINE ANALOGS

Phenylalanine

Tyrosine

NH2

OH

O

NH2

OH

O

OH

Shikimate

path

MEV

Piperine

AAA path

Ephedrine Cathinone

Secologanin

NH2

O

OH

NH

Tryptamine

Dopamine 4-HPAA

H

H

OH

N

O

OH

H

H

OO

O

OO

NO

O

O

O

N

N

N

N

PHENETHYL-

ISOQUINOLINE

ALKALOIDS

Colchicine

L-DOPA

OH

N

N

O

NH

O

O

O

O

O

O

NH2

Vinblastine Quinine Camptothecin

OO

N+

O

O

OH

O

O

OO

OO

O

OH

N

NNH

N

H

H

N

NOH

O

OOH

O

N

N

OOO

N+

O

O

Sparteine

Pyruvate

N

N

O

O O

O

N

H

H

OO

OHN

H

H

O

O

O

N

SIMPLE INDOLES +

β-CARBOLINES

Serotonin

α-Ketoglutarate Glutamate

Arginine

Lysine

Cadaverine

Putrescine

Ornithine

TCA cycle

Harmine

OH

NH2

NH

O NH

N

N

NH

H

Aro3+Aro4

Aro1

Aro2

Aro7

OH

NH



Figure 3. Interfacing plant phenylpropanoid and polyketide secondary metabolic pathways with

microbial metabolism. A selection of natural plant pathways in a prospective S. cerevisiae host is

shown. More extensive networks of natural and synthetic phenylpropanoid routes have been shown

previously (Wang et al., 2015; Zhao et al., 2015). Refer to Figure 1 and Figure 2 for abbreviations and

color coding. Additional abbreviations: Acc1, acetyl-CoA carboxylase; PAL, phenylalanine ammonia-

lyase; TAL, tyrosine ammonia-lyase; PKS, polyketide synthase.

Sugars

PEP E4P

Prephenate

Shikimate

path

Malonyl-CoA

Phenylalanine Tyrosine

NH2

OH

O

NH2

OH

O

OH

OH

O

Cinnamic acidOH

OH

O

p-Coumaric acid

PAL TAL

p-Coumaroyl-CoA

Acc1

COUMARINS

FLAVONOIDS

STILBENOIDS

Naringenin

(flavanone)

OH O

OH O

OH

3 Malonyl-CoA

3 Malonyl-

CoA

OH

OH

OH

Resveratrol

Umbelliferone

Pelargonidin 3-glucoside

(anthocyanin)

Quercetin

(flavonol)

Genistein

(isoflavonoid)

Pinosylvin

Pterostilbene

Pinostilbene

OOH O

O

O

OH

OH

OH

OH

O

OH

PPPGlycolysis

AAA

path

PKS

PKS

Caffeoyl-CoA Feruloyl-CoA

OH

S-CoA

O

Scopoletin

OH

OH

S-CoA

O

Acetyl-CoACoumarin

OO

Esculetin

OH

OOH O

O

OOH O

4-Hydroxycoumarin

OH

OO

Cinnamoyl-CoA

S-CoA

O

PKS3 Malonyl-CoA

OH

OH

OH O

OH O

OH

OH

OH O

OH O GlcO

OH O+

OH

OH

Caffeic acid Ferulic acid

OH

OH

OH

O

OH

O

S-CoA

O

OHOH

O

O

OTHER

PHENOLS

Vanillin

Angelicin

OOO

O

OH

O

Dhydrokaempferol

(dihydroflavonol)

OH

OH O

OH O

OH



Parsed CitationsAbdel-Mawgoud AM, Markham KA, Palmer CM, Liu N, Stephanopoulos G, Alper HS (2018) Metabolic engineering in the host Yarrowialipolytica. Metabolic Engineering (in press)

Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Ahmed SA, Ross SA, Slade D, Radwan MM, Khan IA, ElSohly MA (2015) Minor oxygenated cannabinoids from high potency Cannabissativa L. Phytochemistry 117: 194-199


Aizpurua-Olaizola O, Soydaner U, Ozturk E, Schibano D, Simsir Y, Navarro P, Etxebarria N, Usobiaga A (2016) Evolution of thecannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes. Journal of Natural Products79: 324-331


Ajikumar PK, Xiao W-H, Tyo KE, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoidpathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330: 70-74


Albertsen L, Chen Y, Bach LS, Rattleff S, Maury J, Brix S, Nielsen J, Mortensen UH (2011) Diversion of flux toward sesquiterpeneproduction in Saccharomyces cerevisiae by fusion of host and heterologous enzymes. Applied and Environmental Microbiology 77:1033-1040


Alonso-Gutierrez J, Chan R, Batth TS, Adams PD, Keasling JD, Petzold CJ, Lee TS (2013) Metabolic engineering of Escherichia coli forlimonene and perillyl alcohol production. Metabolic Engineering 19: 33-41


Asadollahi MA, Maury J, Patil KR, Schalk M, Clark A, Nielsen J (2009) Enhancing sesquiterpene production in Saccharomycescerevisiae through in silico driven metabolic engineering. Metabolic Engineering 11: 328-334


Azuma S, Tsunekawa H, Okabe M, Okamoto R, Aiba S (1993) Hyper-production of l-trytophan via fermentation with crystallization.Applied Microbiology and Biotechnology 39: 471-476


Baltz RH (2010) Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters.Journal of Industrial Microbiology & Biotechnology 37: 759-772


Becker JV, Armstrong GO, van der Merwe MJ, Lambrechts MG, Vivier MA, Pretorius IS (2003) Metabolic engineering of Saccharomycescerevisiae for the synthesis of the wine-related antioxidant resveratrol. FEMS Yeast Research 4: 79-85


Biggs BW, Lim CG, Sagliani K, Shankar S, Stephanopoulos G, De Mey M, Ajikumar PK (2016) Overcoming heterologous proteininterdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli. Proceedings of the National Academy ofSciences: 201515826


Billingsley JM, DeNicola AB, Barber JS, Tang M-C, Horecka J, Chu A, Garg NK, Tang Y (2017) Engineering the biocatalytic selectivity ofiridoid production in Saccharomyces cerevisiae. Metabolic Engineering 44: 117-125


Brown S, Clastre M, Courdavault V, O'Connor SE (2015) De novo production of the plant-derived alkaloid strictosidine in yeast.Proceedings of the National Academy of Sciences 112: 3205-3210


Brückner C, Oreb M, Kunze G, Boles E, Tripp J (2018) An expanded enzyme toolbox for production of cis, cis-muconic acid and othershikimate pathway derivatives in Saccharomyces cerevisiae. FEMS Yeast Research 18: foy017

Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from

Copyright © 2019 American Society of Plant Biologists. All rights reserved.

https://www.ncbi.nlm.nih.gov/pubmed?term=Abdel%2DMawgoud AM%2C Markham KA%2C Palmer CM%2C Liu N%2C Stephanopoulos G%2C Alper HS %282018%29 Metabolic engineering in the host Yarrowia lipolytica%2E Metabolic Engineering %28in press&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Abdel-Mawgoud&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering in the host Yarrowia lipolytica.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering in the host Yarrowia lipolytica.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Abdel-Mawgoud&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Ahmed SA%2C Ross SA%2C Slade D%2C Radwan MM%2C Khan IA%2C ElSohly MA %282015%29 Minor oxygenated cannabinoids from high potency Cannabis sativa L%2E Phytochemistry&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ahmed&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Minor oxygenated cannabinoids from high potency Cannabis sativa L&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Minor oxygenated cannabinoids from high potency Cannabis sativa L&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ahmed&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Aizpurua%2DOlaizola O%2C Soydaner U%2C O�?ztu�?rk E%2C Schibano D%2C Simsir Y%2C Navarro P%2C Etxebarria N%2C Usobiaga A %282016%29 Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes%2E Journal of Natural Products&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Aizpurua-Olaizola&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Aizpurua-Olaizola&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Ajikumar PK%2C Xiao W%2DH%2C Tyo KE%2C Wang Y%2C Simeon F%2C Leonard E%2C Mucha O%2C Phon TH%2C Pfeifer B%2C Stephanopoulos G %282010%29 Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli%2E Science&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ajikumar&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ajikumar&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Albertsen L%2C Chen Y%2C Bach LS%2C Rattleff S%2C Maury J%2C Brix S%2C Nielsen J%2C Mortensen UH %282011%29 Diversion of flux toward sesquiterpene production in Saccharomyces cerevisiae by fusion of host and heterologous enzymes%2E Applied and Environmental Microbiology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Albertsen&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Diversion of flux toward sesquiterpene production in Saccharomyces cerevisiae by fusion of host and heterologous enzymes&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Diversion of flux toward sesquiterpene production in Saccharomyces cerevisiae by fusion of host and heterologous enzymes&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Albertsen&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Alonso%2DGutierrez J%2C Chan R%2C Batth TS%2C Adams PD%2C Keasling JD%2C Petzold CJ%2C Lee TS %282013%29 Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Alonso-Gutierrez&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Alonso-Gutierrez&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Asadollahi MA%2C Maury J%2C Patil KR%2C Schalk M%2C Clark A%2C Nielsen J %282009%29 Enhancing sesquiterpene production in Saccharomyces cerevisiae through in silico driven metabolic engineering%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Asadollahi&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Enhancing sesquiterpene production in Saccharomyces cerevisiae through in silico driven metabolic engineering&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Enhancing sesquiterpene production in Saccharomyces cerevisiae through in silico driven metabolic engineering&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Asadollahi&as_ylo=2009&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Azuma S%2C Tsunekawa H%2C Okabe M%2C Okamoto R%2C Aiba S %281993%29 Hyper%2Dproduction of l%2Dtrytophan via fermentation with crystallization%2E Applied Microbiology and Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Azuma&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Hyper-production of l-trytophan via fermentation with crystallization&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Hyper-production of l-trytophan via fermentation with crystallization&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Azuma&as_ylo=1993&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Baltz RH %282010%29 Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters%2E Journal of Industrial Microbiology %26 Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Baltz&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Baltz&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Becker JV%2C Armstrong GO%2C van der Merwe MJ%2C Lambrechts MG%2C Vivier MA%2C Pretorius IS %282003%29 Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine%2Drelated antioxidant resveratrol%2E FEMS Yeast Research&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Becker&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Becker&as_ylo=2003&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Biggs BW%2C Lim CG%2C Sagliani K%2C Shankar S%2C Stephanopoulos G%2C De Mey M%2C Ajikumar PK %282016%29 Overcoming heterologous protein interdependency to optimize P450%2Dmediated Taxol precursor synthesis in Escherichia coli%2E Proceedings of the National Academy of Sciences&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Biggs&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Overcoming heterologous protein interdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Overcoming heterologous protein interdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Biggs&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Billingsley JM%2C DeNicola AB%2C Barber JS%2C Tang M%2DC%2C Horecka J%2C Chu A%2C Garg NK%2C Tang Y %282017%29 Engineering the biocatalytic selectivity of iridoid production in Saccharomyces cerevisiae%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Billingsley&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering the biocatalytic selectivity of iridoid production in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering the biocatalytic selectivity of iridoid production in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Billingsley&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Brown S%2C Clastre M%2C Courdavault V%2C O%27Connor SE %282015%29 De novo production of the plant%2Dderived alkaloid strictosidine in yeast%2E Proceedings of the National Academy of Sciences&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Brown&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=De novo production of the plant-derived alkaloid strictosidine in yeast&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=De novo production of the plant-derived alkaloid strictosidine in yeast&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Brown&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Br�ckner C%2C Oreb M%2C Kunze G%2C Boles E%2C Tripp J %282018%29 An expanded enzyme toolbox for production of cis%2C cis%2Dmuconic acid and other shikimate pathway derivatives in Saccharomyces cerevisiae%2E FEMS Yeast Research 18%3A foy&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Brückner&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=An expanded enzyme toolbox for production of cis, cis-muconic acid and other shikimate pathway derivatives in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=An expanded enzyme toolbox for production of cis, cis-muconic acid and other shikimate pathway derivatives in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Brückner&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1


Google Scholar: Author Only Title Only Author and Title

Camesasca L, Minteguiaga M, Fariña L, Salzman V, Aguilar P, Gaggero C, Carrau F (2018) Overproduction of isoprenoids bySaccharomyces cerevisiae in a synthetic grape juice medium in the absence of plant genes. International Journal of Food Microbiology282: 42-48


Campbell A, Bauchart P, Gold ND, Zhu Y, De Luca V, Martin VJ (2016) Engineering of a nepetalactol-producing platform strain ofSaccharomyces cerevisiae for the production of plant seco-iridoids. ACS synthetic biology 5: 405-414


Canelas AB, Harrison N, Fazio A, Zhang J, Pitkänen J-P, Van den Brink J, Bakker BM, Bogner L, Bouwman J, Castrillo JI (2010)Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains. NatureCommunications 1: 145


Caputi L, Franke J, Farrow SC, Chung K, Payne RM, Nguyen T-D, Dang T-TT, Carqueijeiro IST, Koudounas K, de Bernonville TD (2018)Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. Science 360: 1235-1239


Cardenas J, Da Silva NA (2016) Engineering cofactor and transport mechanisms in Saccharomyces cerevisiae for enhanced acetyl-CoAand polyketide biosynthesis. Metabolic Engineering 36: 80-89


Casini A, Chang F-Y, Eluere R, King AM, Young EM, Dudley QM, Karim A, Pratt K, Bristol C, Forget A (2018) A pressure test to make 10molecules in 90 days: External evaluation of methods to engineer biology. Journal of the American Chemical Society 140: 4302-4316


Chambon C, Ladeveze V, Oulmouden A, Servouse M, Karst F (1990) Isolation and properties of yeast mutants affected in farnesyldiphosphate synthetase. Current Genetics 18: 41-46


Chang MC, Eachus RA, Trieu W, Ro D-K, Keasling JD (2007) Engineering Escherichia coli for production of functionalized terpenoidsusing plant P450s. Nature Chemical Biology 3: 274


Chao R, Mishra S, Si T, Zhao H (2017) Engineering biological systems using automated biofoundries. Metabolic Engineering 42: 98-108Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Chemler JA, Fowler ZL, McHugh KP, Koffas MA (2010) Improving NADPH availability for natural product biosynthesis in Escherichia coliby metabolic engineering. Metabolic Engineering 12: 96-104


Chen X, Yang X, Shen Y, Hou J, Bao X (2017) Increasing malonyl-CoA derived product through controlling the transcription regulatorsof phospholipid synthesis in Saccharomyces cerevisiae. ACS Synthetic Biology 6: 905-912


Chen X, Yang X, Shen Y, Hou J, Bao X (2018) Screening phosphorylation site mutations in yeast acetyl-CoA carboxylase using malonyl-CoA sensor to Improve malonyl-CoA-derived product. Frontiers in microbiology 9: 47


Chen Y, Xiao W, Wang Y, Liu H, Li X, Yuan Y (2016) Lycopene overproduction in Saccharomyces cerevisiae through combining pathwayengineering with host engineering. Microbial Cell Factories 15: 113


Choi JW, Da Silva NA (2014) Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase. Journalof Biotechnology 187: 56-59


Connolly J, Hill R (1991) Dictionary of Terpenes. In. Chapman and HallPubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from


https://www.ncbi.nlm.nih.gov/pubmed?term=Camesasca L%2C Minteguiaga M%2C Fari�a L%2C Salzman V%2C Aguilar P%2C Gaggero C%2C Carrau F %282018%29 Overproduction of isoprenoids by Saccharomyces cerevisiae in a synthetic grape juice medium in the absence of plant genes%2E International Journal of Food Microbiology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Camesasca&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Overproduction of isoprenoids by Saccharomyces cerevisiae in a synthetic grape juice medium in the absence of plant genes&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Overproduction of isoprenoids by Saccharomyces cerevisiae in a synthetic grape juice medium in the absence of plant genes&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Camesasca&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Campbell A%2C Bauchart P%2C Gold ND%2C Zhu Y%2C De Luca V%2C Martin VJ %282016%29 Engineering of a nepetalactol%2Dproducing platform strain of Saccharomyces cerevisiae for the production of plant seco%2Diridoids%2E ACS synthetic biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Campbell&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering of a nepetalactol-producing platform strain of Saccharomyces cerevisiae for the production of plant seco-iridoids&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering of a nepetalactol-producing platform strain of Saccharomyces cerevisiae for the production of plant seco-iridoids&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Campbell&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Canelas AB%2C Harrison N%2C Fazio A%2C Zhang J%2C Pitk�nen J%2DP%2C Van den Brink J%2C Bakker BM%2C Bogner L%2C Bouwman J%2C Castrillo JI %282010%29 Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains%2E Nature Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Canelas&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Canelas&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Caputi L%2C Franke J%2C Farrow SC%2C Chung K%2C Payne RM%2C Nguyen T%2DD%2C Dang T%2DTT%2C Carqueijeiro IST%2C Koudounas K%2C de Bernonville TD %282018%29 Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle%2E Science&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Caputi&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Caputi&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Cardenas J%2C Da Silva NA %282016%29 Engineering cofactor and transport mechanisms in Saccharomyces cerevisiae for enhanced acetyl%2DCoA and polyketide biosynthesis%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Cardenas&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering cofactor and transport mechanisms in Saccharomyces cerevisiae for enhanced acetyl-CoA and polyketide biosynthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering cofactor and transport mechanisms in Saccharomyces cerevisiae for enhanced acetyl-CoA and polyketide biosynthesis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Cardenas&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Casini A%2C Chang F%2DY%2C Eluere R%2C King AM%2C Young EM%2C Dudley QM%2C Karim A%2C Pratt K%2C Bristol C%2C Forget A %282018%29 A pressure test to make 10 molecules in 90 days%3A External evaluation of methods to engineer biology%2E Journal of the American Chemical Society&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Casini&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=A pressure test to make 10 molecules in 90 days: External evaluation of methods to engineer biology&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Casini&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Chambon C%2C Ladeveze V%2C Oulmouden A%2C Servouse M%2C Karst F %281990%29 Isolation and properties of yeast mutants affected in farnesyl diphosphate synthetase%2E Current Genetics&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Chambon&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Isolation and properties of yeast mutants affected in farnesyl diphosphate synthetase&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Isolation and properties of yeast mutants affected in farnesyl diphosphate synthetase&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Chambon&as_ylo=1990&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Chang MC%2C Eachus RA%2C Trieu W%2C Ro D%2DK%2C Keasling JD %282007%29 Engineering Escherichia coli for production of functionalized terpenoids using plant P450s%2E Nature Chemical Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Chang&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering Escherichia coli for production of functionalized terpenoids using plant P450s.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering Escherichia coli for production of functionalized terpenoids using plant P450s.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Chang&as_ylo=2007&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Chao R%2C Mishra S%2C Si T%2C Zhao H %282017%29 Engineering biological systems using automated biofoundries%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Chao&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering biological systems using automated biofoundries&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering biological systems using automated biofoundries&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Chao&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Chemler JA%2C Fowler ZL%2C McHugh KP%2C Koffas MA %282010%29 Improving NADPH availability for natural product biosynthesis in Escherichia coli by metabolic engineering%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Chemler&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Improving NADPH availability for natural product biosynthesis in Escherichia coli by metabolic engineering&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Improving NADPH availability for natural product biosynthesis in Escherichia coli by metabolic engineering&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Chemler&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Chen X%2C Yang X%2C Shen Y%2C Hou J%2C Bao X %282017%29 Increasing malonyl%2DCoA derived product through controlling the transcription regulators of phospholipid synthesis in Saccharomyces cerevisiae%2E ACS Synthetic Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Chen&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Increasing malonyl-CoA derived product through controlling the transcription regulators of phospholipid synthesis in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Increasing malonyl-CoA derived product through controlling the transcription regulators of phospholipid synthesis in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Chen&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Chen X%2C Yang X%2C Shen Y%2C Hou J%2C Bao X %282018%29 Screening phosphorylation site mutations in yeast acetyl%2DCoA carboxylase using malonyl%2DCoA sensor to Improve malonyl%2DCoA%2Dderived product%2E Frontiers in microbiology&dopt=abstract


https://scholar.google.com/scholar?as_q=Screening phosphorylation site mutations in yeast acetyl-CoA carboxylase using malonyl-CoA sensor to Improve malonyl-CoA-derived product.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Screening phosphorylation site mutations in yeast acetyl-CoA carboxylase using malonyl-CoA sensor to Improve malonyl-CoA-derived product.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Chen&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Chen Y%2C Xiao W%2C Wang Y%2C Liu H%2C Li X%2C Yuan Y %282016%29 Lycopene overproduction in Saccharomyces cerevisiae through combining pathway engineering with host engineering%2E Microbial Cell Factories&dopt=abstract


https://scholar.google.com/scholar?as_q=Lycopene overproduction in Saccharomyces cerevisiae through combining pathway engineering with host engineering.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Lycopene overproduction in Saccharomyces cerevisiae through combining pathway engineering with host engineering.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Chen&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Choi JW%2C Da Silva NA %282014%29 Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl%2DCoA carboxylase%2E Journal of Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Choi&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Choi&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Connolly J%2C Hill R %281991%29 Dictionary of Terpenes%2E In%2E Chapman and Hall&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Connolly&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Dictionary of Terpenes.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Dictionary of Terpenes.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Connolly&as_ylo=1991&as_allsubj=all&hl=en&c2coff=1


Davis MS, Solbiati J, Cronan J (2000) Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis inEscherichia coli. Journal of Biological Chemistry 275: 28593-28598


DeLoache WC, Russ ZN, Narcross L, Gonzales AM, Martin VJ, Dueber JE (2015) An enzyme-coupled biosensor enables (S)-reticulineproduction in yeast from glucose. Nature Chemical Biology 11: 465-471


Denby CM, Li RA, Vu VT, Costello Z, Lin W, Chan LJG, Williams J, Donaldson B, Bamforth CW, Petzold CJ (2018) Industrial brewingyeast engineered for the production of primary flavor determinants in hopped beer. Nature Communications 9: 965


Ding M-z, Yan H-f, Li L-f, Zhai F, Shang L-q, Yin Z, Yuan Y-j (2014) Biosynthesis of Taxadiene in Saccharomyces cerevisiae: selection ofgeranylgeranyl diphosphate synthase directed by a computer-aided docking strategy. PloS one 9: e109348


Duan L, Ding W, Liu X, Cheng X, Cai J, Hua E, Jiang H (2017) Biosynthesis and engineering of kaempferol in Saccharomycescerevisiae. Microbial Cell Factories 16: 165


Dudnik A, Almeida AF, Andrade R, Avila B, Bañados P, Barbay D, Bassard J-E, Benkoulouche M, Bott M, Braga A (2018) BacHBerry:BACterial Hosts for production of Bioactive phenolics from bERRY fruits. Phytochemistry Reviews 17: 291-326


Eichenberger M, Hansson A, Fischer D, Dürr L, Naesby M (2018) De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.FEMS Yeast Research 18: foy046


Eichenberger M, Lehka BJ, Folly C, Fischer D, Martens S, Simón E, Naesby M (2017) Metabolic engineering of Saccharomycescerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties. MetabolicEngineering 39: 80-89


Farrow SC, Hagel JM, Beaudoin GA, Burns DC, Facchini PJ (2015) Stereochemical inversion of (S)-reticuline by a cytochrome P450fusion in opium poppy. Nature Chemical Biology 11: 728-732


Fossati E, Ekins A, Narcross L, Zhu Y, Falgueyret J-P, Beaudoin GA, Facchini PJ, Martin VJ (2014) Reconstitution of a 10-gene pathwayfor synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae. Nature Communications 5


Fossati E, Narcross L, Ekins A, Falgueyret J-P, Martin VJ (2015) Synthesis of morphinan alkaloids in Saccharomyces cerevisiae. PloSOne 10: e0124459


Fowler ZL, Gikandi WW, Koffas MA (2009) Increased malonyl coenzyme A biosynthesis by tuning the Escherichia coli metabolic networkand its application to flavanone production. Applied and Environmental Microbiology 75: 5831-5839


Frick S, Ounaroon A, Kutchan TM (2001) Combinatorial biochemistry in plants: the case of O-methyltransferases. Phytochemistry 56: 1-4Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Galanie S, Thodey K, Trenchard IJ, Interrante MF, Smolke CD (2015) Complete biosynthesis of opioids in yeast. Science 349: 1095-1100Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Gao M, Cao M, Suastegui M, Walker J, Rodriguez Quiroz N, Wu Y, Tribby D, Okerlund A, Stanley L, Shanks JV (2016) Innovating anonconventional yeast platform for producing shikimate as the building block of high-value aromatics. ACS Synthetic Biology 6: 29-38



https://www.ncbi.nlm.nih.gov/pubmed?term=Davis MS%2C Solbiati J%2C Cronan J %282000%29 Overproduction of acetyl%2DCoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli%2E Journal of Biological Chemistry&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Davis&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Davis&as_ylo=2000&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=DeLoache WC%2C Russ ZN%2C Narcross L%2C Gonzales AM%2C Martin VJ%2C Dueber JE %282015%29 An enzyme%2Dcoupled biosensor enables %28S%29%2Dreticuline production in yeast from glucose%2E Nature Chemical Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=DeLoache&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=DeLoache&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Denby CM%2C Li RA%2C Vu VT%2C Costello Z%2C Lin W%2C Chan LJG%2C Williams J%2C Donaldson B%2C Bamforth CW%2C Petzold CJ %282018%29 Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer%2E Nature Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Denby&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Denby&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Ding M%2Dz%2C Yan H%2Df%2C Li L%2Df%2C Zhai F%2C Shang L%2Dq%2C Yin Z%2C Yuan Y%2Dj %282014%29 Biosynthesis of Taxadiene in Saccharomyces cerevisiae%3A selection of geranylgeranyl diphosphate synthase directed by a computer%2Daided docking strategy%2E PloS one 9%3A e&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ding&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of Taxadiene in Saccharomyces cerevisiae: selection of geranylgeranyl diphosphate synthase directed by a computer-aided docking strategy.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of Taxadiene in Saccharomyces cerevisiae: selection of geranylgeranyl diphosphate synthase directed by a computer-aided docking strategy.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ding&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Duan L%2C Ding W%2C Liu X%2C Cheng X%2C Cai J%2C Hua E%2C Jiang H %282017%29 Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae%2E Microbial Cell Factories&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Duan&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Duan&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Dudnik A%2C Almeida AF%2C Andrade R%2C Avila B%2C Ba�ados P%2C Barbay D%2C Bassard J%2DE%2C Benkoulouche M%2C Bott M%2C Braga A %282018%29 BacHBerry%3A BACterial Hosts for production of Bioactive phenolics from bERRY fruits%2E Phytochemistry Reviews&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Dudnik&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Dudnik&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Eichenberger M%2C Hansson A%2C Fischer D%2C D�rr L%2C Naesby M %282018%29 De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae%2E FEMS Yeast Research 18%3A foy&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Eichenberger&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Eichenberger&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Eichenberger M%2C Lehka BJ%2C Folly C%2C Fischer D%2C Martens S%2C Sim�n E%2C Naesby M %282017%29 Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant%2C antidiabetic%2C and sweet tasting properties%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Eichenberger&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Eichenberger&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Farrow SC%2C Hagel JM%2C Beaudoin GA%2C Burns DC%2C Facchini PJ %282015%29 Stereochemical inversion of %28S%29%2Dreticuline by a cytochrome P450 fusion in opium poppy%2E Nature Chemical Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Farrow&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Farrow&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Fossati E%2C Ekins A%2C Narcross L%2C Zhu Y%2C Falgueyret J%2DP%2C Beaudoin GA%2C Facchini PJ%2C Martin VJ %282014%29 Reconstitution of a 10%2Dgene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae%2E Nature Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Fossati&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Fossati&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Fossati E%2C Narcross L%2C Ekins A%2C Falgueyret J%2DP%2C Martin VJ %282015%29 Synthesis of morphinan alkaloids in Saccharomyces cerevisiae%2E PloS One 10%3A e&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Fossati&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Synthesis of morphinan alkaloids in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Synthesis of morphinan alkaloids in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Fossati&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Fowler ZL%2C Gikandi WW%2C Koffas MA %282009%29 Increased malonyl coenzyme A biosynthesis by tuning the Escherichia coli metabolic network and its application to flavanone production%2E Applied and Environmental Microbiology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Fowler&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Increased malonyl coenzyme A biosynthesis by tuning the Escherichia coli metabolic network and its application to flavanone production&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Increased malonyl coenzyme A biosynthesis by tuning the Escherichia coli metabolic network and its application to flavanone production&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Fowler&as_ylo=2009&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Frick S%2C Ounaroon A%2C Kutchan TM %282001%29 Combinatorial biochemistry in plants%3A the case of O%2Dmethyltransferases%2E Phytochemistry&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Frick&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Combinatorial biochemistry in plants: the case of O-methyltransferases&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Combinatorial biochemistry in plants: the case of O-methyltransferases&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Frick&as_ylo=2001&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Galanie S%2C Thodey K%2C Trenchard IJ%2C Interrante MF%2C Smolke CD %282015%29 Complete biosynthesis of opioids in yeast%2E Science&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Galanie&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Complete biosynthesis of opioids in yeast&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Complete biosynthesis of opioids in yeast&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Galanie&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Gao M%2C Cao M%2C Suastegui M%2C Walker J%2C Rodriguez Quiroz N%2C Wu Y%2C Tribby D%2C Okerlund A%2C Stanley L%2C Shanks JV %282016%29 Innovating a nonconventional yeast platform for producing shikimate as the building block of high%2Dvalue aromatics%2E ACS Synthetic Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Gao&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Innovating a nonconventional yeast platform for producing shikimate as the building block of high-value aromatics&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Innovating a nonconventional yeast platform for producing shikimate as the building block of high-value aromatics&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Gao&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1


Gaspar P, Carvalho AL, Vinga S, Santos H, Neves AR (2013) From physiology to systems metabolic engineering for the production ofbiochemicals by lactic acid bacteria. Biotechnology Advances 31: 764-788


Geu-Flores F, Sherden NH, Courdavault V, Burlat V, Glenn WS, Wu C, Nims E, Cui Y, O'connor SE (2012) An alternative route to cyclicterpenes by reductive cyclization in iridoid biosynthesis. Nature 492: 138


Glenn WS, Runguphan W, O'Connor SE (2013) Recent progress in the metabolic engineering of alkaloids in plant systems. CurrentOpinion in Biotechnology 24: 354-365


Gold ND, Gowen CM, Lussier F-X, Cautha SC, Mahadevan R, Martin VJ (2015) Metabolic engineering of a tyrosine-overproducing yeastplatform using targeted metabolomics. Microbial cell factories 14: 1


Hagel JM, Krizevski R, Marsolais F, Lewinsohn E, Facchini PJ (2012) Biosynthesis of amphetamine analogs in plants. Trends in PlantScience 17: 404-412


Hausjell J, Halbwirth H, Spadiut O (2018) Recombinant production of eukaryotic cytochrome P450s in microbial cell factories.Bioscience Reports: BSR20171290


Hawkins KM, Smolke CD (2008) Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae. Nature Chemical Biology 4:564-573


Hazelwood LA, Daran J-M, van Maris AJ, Pronk JT, Dickinson JR (2008) The Ehrlich pathway for fusel alcohol production: a century ofresearch on Saccharomyces cerevisiae metabolism. Applied and Environmental Microbiology 74: 2259-2266


Heo KT, Kang S-Y, Hong Y-S (2017) De novo biosynthesis of pterostilbene in an Escherichia coli strain using a new resveratrol O-methyltransferase from Arabidopsis. Microbial Cell Factories 16: 30


Horwitz AA, Walter JM, Schubert MG, Kung SH, Hawkins K, Platt DM, Hernday AD, Mahatdejkul-Meadows T, Szeto W, Chandran SS(2015) Efficient multiplexed integration of synergistic alleles and metabolic pathways in yeasts via CRISPR-Cas. Cell Systems


Ignea C, Cvetkovic I, Loupassaki S, Kefalas P, Johnson CB, Kampranis SC, Makris AM (2011) Improving yeast strains using recyclableintegration cassettes, for the production of plant terpenoids. Microbial Cell Factories 10: 4


Ikeda M, Ozaki A, Katsumata R (1993) Phenylalanine production by metabolically engineered Corynebacterium glutamicum with thepheA gene of Escherichia coli. Applied Microbiology and Biotechnology 39: 318-323


Jakočiūnas T, Bonde I, Herrgård M, Harrison SJ, Kristensen M, Pedersen LE, Jensen MK, Keasling JD (2015) Multiplex metabolicpathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae. Metabolic Engineering 28: 213-222


Jakočiūnas T, Jensen MK, Keasling JD (2017) System-level perturbations of cell metabolism using CRISPR/Cas9. Current Opinion inBiotechnology 46: 134-140


Jiang G-Z, Yao M-D, Wang Y, Zhou L, Song T-Q, Liu H, Xiao W-H, Yuan Y-J (2017) Manipulation of GES and ERG20 for geranioloverproduction in Saccharomyces cerevisiae. Metabolic Engineering 41: 57-66



https://www.ncbi.nlm.nih.gov/pubmed?term=Gaspar P%2C Carvalho AL%2C Vinga S%2C Santos H%2C Neves AR %282013%29 From physiology to systems metabolic engineering for the production of biochemicals by lactic acid bacteria%2E Biotechnology Advances&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Gaspar&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=From physiology to systems metabolic engineering for the production of biochemicals by lactic acid bacteria&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=From physiology to systems metabolic engineering for the production of biochemicals by lactic acid bacteria&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Gaspar&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Geu%2DFlores F%2C Sherden NH%2C Courdavault V%2C Burlat V%2C Glenn WS%2C Wu C%2C Nims E%2C Cui Y%2C O%27connor SE %282012%29 An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis%2E Nature&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Geu-Flores&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Geu-Flores&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Glenn WS%2C Runguphan W%2C O%27Connor SE %282013%29 Recent progress in the metabolic engineering of alkaloids in plant systems%2E Current Opinion in Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Glenn&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Recent progress in the metabolic engineering of alkaloids in plant systems&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Recent progress in the metabolic engineering of alkaloids in plant systems&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Glenn&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Gold ND%2C Gowen CM%2C Lussier F%2DX%2C Cautha SC%2C Mahadevan R%2C Martin VJ %282015%29 Metabolic engineering of a tyrosine%2Doverproducing yeast platform using targeted metabolomics%2E Microbial cell factories&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Gold&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of a tyrosine-overproducing yeast platform using targeted metabolomics.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of a tyrosine-overproducing yeast platform using targeted metabolomics.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Gold&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Hagel JM%2C Krizevski R%2C Marsolais F%2C Lewinsohn E%2C Facchini PJ %282012%29 Biosynthesis of amphetamine analogs in plants%2E Trends in Plant Science&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Hagel&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of amphetamine analogs in plants&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of amphetamine analogs in plants&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Hagel&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Hausjell J%2C Halbwirth H%2C Spadiut O %282018%29 Recombinant production of eukaryotic cytochrome P450s in microbial cell factories%2E Bioscience Reports%3A BSR&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Hausjell&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Recombinant production of eukaryotic cytochrome P450s in microbial cell factories.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Recombinant production of eukaryotic cytochrome P450s in microbial cell factories.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Hausjell&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Hawkins KM%2C Smolke CD %282008%29 Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae%2E Nature Chemical Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Hawkins&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Hawkins&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Hazelwood LA%2C Daran J%2DM%2C van Maris AJ%2C Pronk JT%2C Dickinson JR %282008%29 The Ehrlich pathway for fusel alcohol production%3A a century of research on Saccharomyces cerevisiae metabolism%2E Applied and Environmental Microbiology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Hazelwood&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Hazelwood&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Heo KT%2C Kang S%2DY%2C Hong Y%2DS %282017%29 De novo biosynthesis of pterostilbene in an Escherichia coli strain using a new resveratrol O%2Dmethyltransferase from Arabidopsis%2E Microbial Cell Factories&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Heo&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=De novo biosynthesis of pterostilbene in an Escherichia coli strain using a new resveratrol O-methyltransferase from Arabidopsis.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=De novo biosynthesis of pterostilbene in an Escherichia coli strain using a new resveratrol O-methyltransferase from Arabidopsis.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Heo&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Horwitz AA%2C Walter JM%2C Schubert MG%2C Kung SH%2C Hawkins K%2C Platt DM%2C Hernday AD%2C Mahatdejkul%2DMeadows T%2C Szeto W%2C Chandran SS %282015%29 Efficient multiplexed integration of synergistic alleles and metabolic pathways in yeasts via CRISPR%2DCas%2E Cell Systems&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Horwitz&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Efficient multiplexed integration of synergistic alleles and metabolic pathways in yeasts via CRISPR-Cas.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Efficient multiplexed integration of synergistic alleles and metabolic pathways in yeasts via CRISPR-Cas.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Horwitz&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Ignea C%2C Cvetkovic I%2C Loupassaki S%2C Kefalas P%2C Johnson CB%2C Kampranis SC%2C Makris AM %282011%29 Improving yeast strains using recyclable integration cassettes%2C for the production of plant terpenoids%2E Microbial Cell Factories&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ignea&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Improving yeast strains using recyclable integration cassettes, for the production of plant terpenoids.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Improving yeast strains using recyclable integration cassettes, for the production of plant terpenoids.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ignea&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Ikeda M%2C Ozaki A%2C Katsumata R %281993%29 Phenylalanine production by metabolically engineered Corynebacterium glutamicum with the pheA gene of Escherichia coli%2E Applied Microbiology and Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ikeda&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Phenylalanine production by metabolically engineered Corynebacterium glutamicum with the pheA gene of Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Phenylalanine production by metabolically engineered Corynebacterium glutamicum with the pheA gene of Escherichia coli&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ikeda&as_ylo=1993&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Jakočiūnas T%2C Bonde I%2C Herrgård M%2C Harrison SJ%2C Kristensen M%2C Pedersen LE%2C Jensen MK%2C Keasling JD %282015%29 Multiplex metabolic pathway engineering using CRISPR%2FCas9 in Saccharomyces cerevisiae%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Jako�?�i�?«nas&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Jako�?�i�?«nas&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Jakočiūnas T%2C Jensen MK%2C Keasling JD %282017%29 System%2Dlevel perturbations of cell metabolism using CRISPR%2FCas9%2E Current Opinion in Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Jako�?�i�?«nas&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=System-level perturbations of cell metabolism using CRISPR/Cas9&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=System-level perturbations of cell metabolism using CRISPR/Cas9&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Jako�?�i�?«nas&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Jiang G%2DZ%2C Yao M%2DD%2C Wang Y%2C Zhou L%2C Song T%2DQ%2C Liu H%2C Xiao W%2DH%2C Yuan Y%2DJ %282017%29 Manipulation of GES and ERG20 for geraniol overproduction in Saccharomyces cerevisiae%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Jiang&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Manipulation of GES and ERG20 for geraniol overproduction in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Manipulation of GES and ERG20 for geraniol overproduction in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Jiang&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1


Jones J, Vernacchio V, Collins S, Shirke A, Xiu Y, Englaender J, Cress B, McCutcheon C, Linhardt R, Gross R (2017) Completebiosynthesis of anthocyanins using E. coli polycultures. 8


Jongedijk E, Cankar K, Ranzijn J, Krol S, Bouwmeester H, Beekwilder J (2015) Capturing of the monoterpene olefin limoneneproduced in Saccharomyces cerevisiae. Yeast 32: 159-171


Kai K, Mizutani M, Kawamura N, Yamamoto R, Tamai M, Yamaguchi H, Sakata K, Shimizu Bi (2008) Scopoletin is biosynthesized viaortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana. The Plant Journal 55: 989-999


Kallscheuer N, Classen T, Drepper T, Marienhagen J (2019) Production of plant metabolites with applications in the food industryusing engineered microorganisms. Current Opinion in Biotechnology 56: 7-17


Kaneko M, Hwang EI, Ohnishi Y, Horinouchi S (2003) Heterologous production of flavanones in Escherichia coli: potential forcombinatorial biosynthesis of flavonoids in bacteria. Journal of Industrial Microbiology and Biotechnology 30: 456-461


Kang S-Y, Lee JK, Choi O, Kim CY, Jang J-H, Hwang BY, Hong Y-S (2014) Biosynthesis of methylated resveratrol analogs through theconstruction of an artificial biosynthetic pathway in E. coli. BMC Biotechnology 14: 67


Katz M, Forster J, David H, Schmidt HP, Sendelius M, Bjorn SP, Durhuus TT (2017) Metabolically engineered cells for the productionof pinosylvin. In. Google Patents


Katz MP, Durhuus T, Smits HP, Förster J (2017) Production of metabolites. In. Google PatentsPubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

King JR, Woolston BM, Stephanopoulos G (2017) Designing a new entry point into isoprenoid metabolism by exploiting fructose-6-phosphate aldolase side reactivity of Escherichia coli. ACS Synthetic Biology 6: 1416-1426


Kita T, Imai S, Sawada H, Kumagai H, Seto H (2008) The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealedby 13C-labeled precursors. Bioscience, Biotechnology, and Biochemistry 72: 1789-1798


Kozak BU, van Rossum HM, Benjamin KR, Wu L, Daran J-MG, Pronk JT, van Maris AJ (2014) Replacement of the Saccharomycescerevisiae acetyl-CoA synthetases by alternative pathways for cytosolic acetyl-CoA synthesis. Metabolic Engineering 21: 46-59


Kozak BU, van Rossum HM, Luttik MA, Akeroyd M, Benjamin KR, Wu L, de Vries S, Daran J-M, Pronk JT, van Maris AJ (2014)Engineering acetyl coenzyme A supply: functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol ofSaccharomyces cerevisiae. MBio 5: e01696-01614


Kozak BU, van Rossum HM, Niemeijer MS, van Dijk M, Benjamin K, Wu L, Daran J-MG, Pronk JT, van Maris AJ (2016) Replacement ofthe initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase.FEMS Yeast Research 16


Lange BM, Ahkami A (2013) Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes-current status and futureopportunities. Plant Biotechnology Journal 11: 169-196


Lee ME, DeLoache WC, Cervantes B, Dueber JE (2015) A highly characterized yeast toolkit for modular, multipart assembly. ACSSynthetic Biology 4: 975-986

Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from


https://www.ncbi.nlm.nih.gov/pubmed?term=Jones J%2C Vernacchio V%2C Collins S%2C Shirke A%2C Xiu Y%2C Englaender J%2C Cress B%2C McCutcheon C%2C Linhardt R%2C Gross R %282017%29 Complete biosynthesis of anthocyanins using E%2E coli polycultures&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Jones&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Complete biosynthesis of anthocyanins using E.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Complete biosynthesis of anthocyanins using E.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Jones&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Jongedijk E%2C Cankar K%2C Ranzijn J%2C Krol S%2C Bouwmeester H%2C Beekwilder J %282015%29 Capturing of the monoterpene olefin limonene produced in Saccharomyces cerevisiae%2E Yeast&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Jongedijk&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Capturing of the monoterpene olefin limonene produced in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Capturing of the monoterpene olefin limonene produced in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Jongedijk&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

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https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Kai&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Scopoletin is biosynthesized via ortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Scopoletin is biosynthesized via ortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kai&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Kallscheuer N%2C Classen T%2C Drepper T%2C Marienhagen J %282019%29 Production of plant metabolites with applications in the food industry using engineered microorganisms%2E Current Opinion in Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Kallscheuer&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Production of plant metabolites with applications in the food industry using engineered microorganisms&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Production of plant metabolites with applications in the food industry using engineered microorganisms&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kallscheuer&as_ylo=2019&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Kaneko M%2C Hwang EI%2C Ohnishi Y%2C Horinouchi S %282003%29 Heterologous production of flavanones in Escherichia coli%3A potential for combinatorial biosynthesis of flavonoids in bacteria%2E Journal of Industrial Microbiology and Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Kaneko&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Heterologous production of flavanones in Escherichia coli: potential for combinatorial biosynthesis of flavonoids in bacteria&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Heterologous production of flavanones in Escherichia coli: potential for combinatorial biosynthesis of flavonoids in bacteria&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kaneko&as_ylo=2003&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Kang S%2DY%2C Lee JK%2C Choi O%2C Kim CY%2C Jang J%2DH%2C Hwang BY%2C Hong Y%2DS %282014%29 Biosynthesis of methylated resveratrol analogs through the construction of an artificial biosynthetic pathway in E%2E coli%2E BMC Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Kang&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of methylated resveratrol analogs through the construction of an artificial biosynthetic pathway in E.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of methylated resveratrol analogs through the construction of an artificial biosynthetic pathway in E.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kang&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Katz M%2C Forster J%2C David H%2C Schmidt HP%2C Sendelius M%2C Bjorn SP%2C Durhuus TT %282017%29 Metabolically engineered cells for the production of pinosylvin%2E In%2E Google Patents&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Katz&hl=en&c2coff=1

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https://www.ncbi.nlm.nih.gov/pubmed?term=King JR%2C Woolston BM%2C Stephanopoulos G %282017%29 Designing a new entry point into isoprenoid metabolism by exploiting fructose%2D6%2Dphosphate aldolase side reactivity of Escherichia coli%2E ACS Synthetic Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=King&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Designing a new entry point into isoprenoid metabolism by exploiting fructose-6-phosphate aldolase side reactivity of Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Designing a new entry point into isoprenoid metabolism by exploiting fructose-6-phosphate aldolase side reactivity of Escherichia coli&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=King&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Kita T%2C Imai S%2C Sawada H%2C Kumagai H%2C Seto H %282008%29 The biosynthetic pathway of curcuminoid in turmeric %28Curcuma longa%29 as revealed by 13C%2Dlabeled precursors%2E Bioscience%2C Biotechnology%2C and Biochemistry&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Kita&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealed by 13C-labeled precursors&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealed by 13C-labeled precursors&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kita&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Kozak BU%2C van Rossum HM%2C Benjamin KR%2C Wu L%2C Daran J%2DMG%2C Pronk JT%2C van Maris AJ %282014%29 Replacement of the Saccharomyces cerevisiae acetyl%2DCoA synthetases by alternative pathways for cytosolic acetyl%2DCoA synthesis%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Kozak&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Replacement of the Saccharomyces cerevisiae acetyl-CoA synthetases by alternative pathways for cytosolic acetyl-CoA synthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Replacement of the Saccharomyces cerevisiae acetyl-CoA synthetases by alternative pathways for cytosolic acetyl-CoA synthesis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kozak&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Kozak BU%2C van Rossum HM%2C Luttik MA%2C Akeroyd M%2C Benjamin KR%2C Wu L%2C de Vries S%2C Daran J%2DM%2C Pronk JT%2C van Maris AJ %282014%29 Engineering acetyl coenzyme A supply%3A functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol of Saccharomyces cerevisiae%2E MBio 5%3A e&dopt=abstract


https://scholar.google.com/scholar?as_q=Engineering acetyl coenzyme A supply: functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol of Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering acetyl coenzyme A supply: functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol of Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kozak&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Kozak BU%2C van Rossum HM%2C Niemeijer MS%2C van Dijk M%2C Benjamin K%2C Wu L%2C Daran J%2DMG%2C Pronk JT%2C van Maris AJ %282016%29 Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP%2Dindependent acetylating acetaldehyde dehydrogenase%2E FEMS Yeast Research&dopt=abstract


https://scholar.google.com/scholar?as_q=Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Kozak&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Lange BM%2C Ahkami A %282013%29 Metabolic engineering of plant monoterpenes%2C sesquiterpenes and diterpenes%2Dcurrent status and future opportunities%2E Plant Biotechnology Journal&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Lange&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes-current status and future opportunities&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes-current status and future opportunities&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lange&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Lee ME%2C DeLoache WC%2C Cervantes B%2C Dueber JE %282015%29 A highly characterized yeast toolkit for modular%2C multipart assembly%2E ACS Synthetic Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Lee&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=A highly characterized yeast toolkit for modular, multipart assembly&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=A highly characterized yeast toolkit for modular, multipart assembly&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lee&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1


Google Scholar: Author Only Title Only Author and Title

Lehka BJ, Eichenberger M, Bjørn-Yoshimoto WE, Vanegas KG, Buijs N, Jensen NB, Dyekjær JD, Jenssen H, Simon E, Naesby M (2016)Improving heterologous production of phenylpropanoids in Saccharomyces cerevisiae by tackling an unwanted side reaction of Tsc13,an endogenous double-bond reductase. FEMS Yeast Research 17: fox004


Leonard E, Lim K-H, Saw P-N, Koffas MA (2007) Engineering central metabolic pathways for high-level flavonoid production inEscherichia coli. Applied and Environmental Microbiology 73: 3877-3886


Leonard E, Yan Y, Fowler ZL, Li Z, Lim C-G, Lim K-H, Koffas MA (2008) Strain improvement of recombinant Escherichia coli for efficientproduction of plant flavonoids. Molecular Pharmaceutics 5: 257-265


Levisson M, Patinios C, Hein S, de Groot PA, Daran J-M, Hall RD, Martens S, Beekwilder J (2018) Engineering de novo anthocyaninproduction in Saccharomyces cerevisiae. Microbial Cell Factories 17: 103


Li C, Ying L-Q, Zhang S-S, Chen N, Liu W-F, Tao Y (2015) Modification of targets related to the Entner–Doudoroff/pentose phosphatepathway route for methyl-d-erythritol 4-phosphate-dependent carotenoid biosynthesis in Escherichia coli. Microbial Cell Factories 14:117


Li J, Lee E-J, Chang L, Facchini PJ (2016) Genes encoding norcoclaurine synthase occur as tandem fusions in the Papaveraceae.Scientific Reports 6: 39256


Li M, Schneider K, Kristensen M, Borodina I, Nielsen J (2016) Engineering yeast for high-level production of stilbenoid antioxidants.Scientific Reports 6: 36827


Li Y, Li S, Thodey K, Trenchard I, Cravens A, Smolke CD (2018) Complete biosynthesis of noscapine and halogenated alkaloids inyeast. Proceedings of the National Academy of Sciences 115: E3922-E3931


Lian J, HamediRad M, Hu S, Zhao H (2017) Combinatorial metabolic engineering using an orthogonal tri-functional CRISPR system.Nature Communications 8: 1688


Liang J-l, Guo L-q, Lin J-f, He Z-q, Cai F-j, Chen J-f (2016) A novel process for obtaining pinosylvin using combinatorial bioengineeringin Escherichia coli. World Journal of Microbiology and Biotechnology 32: 102


Lichman BR, Zhao J, Hailes HC, Ward JM (2017) Enzyme catalysed Pictet-Spengler formation of chiral 1, 1'-disubstituted-and spiro-tetrahydroisoquinolines. Nature Communications 8: 14883


Lin Y, Shen X, Yuan Q, Yan Y (2013) Microbial biosynthesis of the anticoagulant precursor 4-hydroxycoumarin. Nature Communications4: 2603


Liu M, Ding Y, Chen H, Zhao Z, Liu H, Xian M, Zhao G (2017) Improving the production of acetyl-CoA-derived chemicals in Escherichiacoli BL21 (DE3) through iclR and arcA deletion. BMC Microbiology 17: 10


Liu W, Xu X, Zhang R, Cheng T, Cao Y, Li X, Guo J, Liu H, Xian M (2016) Engineering Escherichia coli for high-yield geraniol productionwith biotransformation of geranyl acetate to geraniol under fed-batch culture. Biotechnology for biofuels 9: 58


Liu W, Zhang B, Jiang R (2017) Improving acetyl-CoA biosynthesis in Saccharomyces cerevisiae via the overexpression of www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from


https://www.ncbi.nlm.nih.gov/pubmed?term=Lehka BJ%2C Eichenberger M%2C Bj�rn%2DYoshimoto WE%2C Vanegas KG%2C Buijs N%2C Jensen NB%2C Dyekj�r JD%2C Jenssen H%2C Simon E%2C Naesby M %282016%29 Improving heterologous production of phenylpropanoids in Saccharomyces cerevisiae by tackling an unwanted side reaction of Tsc13%2C an endogenous double%2Dbond reductase%2E FEMS Yeast Research 17%3A fox&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Lehka&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lehka&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Leonard E%2C Lim K%2DH%2C Saw P%2DN%2C Koffas MA %282007%29 Engineering central metabolic pathways for high%2Dlevel flavonoid production in Escherichia coli%2E Applied and Environmental Microbiology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Leonard&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering central metabolic pathways for high-level flavonoid production in Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering central metabolic pathways for high-level flavonoid production in Escherichia coli&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Leonard&as_ylo=2007&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Leonard E%2C Yan Y%2C Fowler ZL%2C Li Z%2C Lim C%2DG%2C Lim K%2DH%2C Koffas MA %282008%29 Strain improvement of recombinant Escherichia coli for efficient production of plant flavonoids%2E Molecular Pharmaceutics&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Leonard&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Strain improvement of recombinant Escherichia coli for efficient production of plant flavonoids&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Strain improvement of recombinant Escherichia coli for efficient production of plant flavonoids&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Leonard&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Levisson M%2C Patinios C%2C Hein S%2C de Groot PA%2C Daran J%2DM%2C Hall RD%2C Martens S%2C Beekwilder J %282018%29 Engineering de novo anthocyanin production in Saccharomyces cerevisiae%2E Microbial Cell Factories&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Levisson&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering de novo anthocyanin production in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering de novo anthocyanin production in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Levisson&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Li C%2C Ying L%2DQ%2C Zhang S%2DS%2C Chen N%2C Liu W%2DF%2C Tao Y %282015%29 Modification of targets related to the Entner%26%23x2013%3BDoudoroff%2Fpentose phosphate pathway route for methyl%2Dd%2Derythritol 4%2Dphosphate%2Ddependent carotenoid biosynthesis in Escherichia coli%2E Microbial Cell Factories&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Li&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Modification of targets related to the Entner?Doudoroff/pentose phosphate pathway route for methyl-d-erythritol 4-phosphate-dependent carotenoid biosynthesis in Escherichia coli.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Modification of targets related to the Entner?Doudoroff/pentose phosphate pathway route for methyl-d-erythritol 4-phosphate-dependent carotenoid biosynthesis in Escherichia coli.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Li&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Li J%2C Lee E%2DJ%2C Chang L%2C Facchini PJ %282016%29 Genes encoding norcoclaurine synthase occur as tandem fusions in the Papaveraceae%2E Scientific Reports&dopt=abstract


https://scholar.google.com/scholar?as_q=Genes encoding norcoclaurine synthase occur as tandem fusions in the Papaveraceae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Genes encoding norcoclaurine synthase occur as tandem fusions in the Papaveraceae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Li&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Li M%2C Schneider K%2C Kristensen M%2C Borodina I%2C Nielsen J %282016%29 Engineering yeast for high%2Dlevel production of stilbenoid antioxidants%2E Scientific Reports&dopt=abstract


https://scholar.google.com/scholar?as_q=Engineering yeast for high-level production of stilbenoid antioxidants.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering yeast for high-level production of stilbenoid antioxidants.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Li&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Li Y%2C Li S%2C Thodey K%2C Trenchard I%2C Cravens A%2C Smolke CD %282018%29 Complete biosynthesis of noscapine and halogenated alkaloids in yeast%2E Proceedings of the National Academy of Sciences 115%3A E3922%2DE&dopt=abstract


https://scholar.google.com/scholar?as_q=Complete biosynthesis of noscapine and halogenated alkaloids in yeast&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Complete biosynthesis of noscapine and halogenated alkaloids in yeast&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Li&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Lian J%2C HamediRad M%2C Hu S%2C Zhao H %282017%29 Combinatorial metabolic engineering using an orthogonal tri%2Dfunctional CRISPR system%2E Nature Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Lian&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Combinatorial metabolic engineering using an orthogonal tri-functional CRISPR system.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Combinatorial metabolic engineering using an orthogonal tri-functional CRISPR system.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lian&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Liang J%2Dl%2C Guo L%2Dq%2C Lin J%2Df%2C He Z%2Dq%2C Cai F%2Dj%2C Chen J%2Df %282016%29 A novel process for obtaining pinosylvin using combinatorial bioengineering in Escherichia coli%2E World Journal of Microbiology and Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Liang&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=A novel process for obtaining pinosylvin using combinatorial bioengineering in Escherichia coli.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=A novel process for obtaining pinosylvin using combinatorial bioengineering in Escherichia coli.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Liang&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Lichman BR%2C Zhao J%2C Hailes HC%2C Ward JM %282017%29 Enzyme catalysed Pictet%2DSpengler formation of chiral 1%2C 1%27%2Ddisubstituted%2Dand spiro%2Dtetrahydroisoquinolines%2E Nature Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Lichman&hl=en&c2coff=1


https://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lichman&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Lin Y%2C Shen X%2C Yuan Q%2C Yan Y %282013%29 Microbial biosynthesis of the anticoagulant precursor 4%2Dhydroxycoumarin%2E Nature Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Lin&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Microbial biosynthesis of the anticoagulant precursor 4-hydroxycoumarin.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Microbial biosynthesis of the anticoagulant precursor 4-hydroxycoumarin.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lin&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Liu M%2C Ding Y%2C Chen H%2C Zhao Z%2C Liu H%2C Xian M%2C Zhao G %282017%29 Improving the production of acetyl%2DCoA%2Dderived chemicals in Escherichia coli BL21 %28DE3%29 through iclR and arcA deletion%2E BMC Microbiology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Liu&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Improving the production of acetyl-CoA-derived chemicals in Escherichia coli BL21 (DE3) through iclR and arcA deletion.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Improving the production of acetyl-CoA-derived chemicals in Escherichia coli BL21 (DE3) through iclR and arcA deletion.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Liu&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Liu W%2C Xu X%2C Zhang R%2C Cheng T%2C Cao Y%2C Li X%2C Guo J%2C Liu H%2C Xian M %282016%29 Engineering Escherichia coli for high%2Dyield geraniol production with biotransformation of geranyl acetate to geraniol under fed%2Dbatch culture%2E Biotechnology for biofuels&dopt=abstract


https://scholar.google.com/scholar?as_q=Engineering Escherichia coli for high-yield geraniol production with biotransformation of geranyl acetate to geraniol under fed-batch culture.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering Escherichia coli for high-yield geraniol production with biotransformation of geranyl acetate to geraniol under fed-batch culture.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Liu&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1


pantothenate kinase and PDH bypass. Biotechnology for biofuels 10: 41Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Liu X, Cheng J, Zhang G, Ding W, Duan L, Yang J, Kui L, Cheng X, Ruan J, Fan W (2018) Engineering yeast for the production ofbreviscapine by genomic analysis and synthetic biology approaches. Nature Communications 9: 448


Lussier F-X, Colatriano D, Wiltshire Z, Page JE, Martin VJ (2012) Engineering microbes for plant polyketide biosynthesis. Computationaland structural biotechnology journal 3: e201210020


Luttik M, Vuralhan Z, Suir E, Braus G, Pronk J, Daran J (2008) Alleviation of feedback inhibition in Saccharomyces cerevisiae aromaticamino acid biosynthesis: quantification of metabolic impact. Metabolic engineering 10: 141-153


Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003) Engineering a mevalonate pathway in Escherichia coli for productionof terpenoids. Nature biotechnology 21: 796-802


Matasci N, Hung L-H, Yan Z, Carpenter EJ, Wickett NJ, Mirarab S, Nguyen N, Warnow T, Ayyampalayam S, Barker M (2014) Data accessfor the 1,000 Plants (1KP) project. GigaScience 3: 1-10


Matsumura E, Nakagawa A, Tomabechi Y, Ikushiro S, Sakaki T, Katayama T, Yamamoto K, Kumagai H, Sato F, Minami H (2018) Microbialproduction of novel sulphated alkaloids for drug discovery. Scientific Reports 8: 7980


Meadows AL, Hawkins KM, Tsegaye Y, Antipov E, Kim Y, Raetz L, Dahl RH, Tai A, Mahatdejkul-Meadows T, Xu L (2016) Rewriting yeastcentral carbon metabolism for industrial isoprenoid production. Nature 537: 694-697


Mendez‐Perez D, Alonso‐Gutierrez J, Hu Q, Molinas M, Baidoo EE, Wang G, Chan LJ, Adams PD, Petzold CJ, Keasling JD (2017)Production of jet fuel precursor monoterpenoids from engineered Escherichia coli. Biotechnology and Bioengineering 114: 1703-1712


Meunier B, de Visser SP, Shaik S (2004) Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes. Chemical Reviews104: 3947-3980


Miettinen K, Dong L, Navrot N, Schneider T, Burlat V, Pollier J, Woittiez L, van der Krol S, Lugan R, Ilc T (2014) The seco-iridoidpathway from Catharanthus roseus. Nature communications 5


Morris JS, Groves RA, Hagel JM, Facchini PJ (2018) An N-methyltransferase from Ephedra sinica catalyzing the formation of ephedrineand pseudoephedrine enables microbial phenylalkylamine production. Journal of Biological Chemistry: jbc. RA118. 004067


Munro AW, Leys DG, McLean KJ, Marshall KR, Ost TW, Daff S, Miles CS, Chapman SK, Lysek DA, Moser CC (2002) P450 BM3: the verymodel of a modern flavocytochrome. Trends in Biochemical Sciences 27: 250-257


Nakagawa A, Matsumura E, Koyanagi T, Katayama T, Kawano N, Yoshimatsu K, Yamamoto K, Kumagai H, Sato F, Minami H (2016) Totalbiosynthesis of opiates by stepwise fermentation using engineered Escherichia coli. Nature communications 7


Nakagawa A, Matsuzaki C, Matsumura E, Koyanagi T, Katayama T, Yamamoto K, Sato F, Kumagai H, Minami H (2014) (R, S)-tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli. Scientific reports 4: 6695


Nakagawa A, Minami H, Kim J-S, Koyanagi T, Katayama T, Sato F, Kumagai H (2011) A bacterial platform for fermentative production of www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from Copyright © 2019 American Society of Plant Biologists. All rights reserved.

https://www.ncbi.nlm.nih.gov/pubmed?term=Liu W%2C Zhang B%2C Jiang R %282017%29 Improving acetyl%2DCoA biosynthesis in Saccharomyces cerevisiae via the overexpression of pantothenate kinase and PDH bypass%2E Biotechnology for biofuels&dopt=abstract


https://scholar.google.com/scholar?as_q=Improving acetyl-CoA biosynthesis in Saccharomyces cerevisiae via the overexpression of pantothenate kinase and PDH bypass.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Improving acetyl-CoA biosynthesis in Saccharomyces cerevisiae via the overexpression of pantothenate kinase and PDH bypass.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Liu&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Liu X%2C Cheng J%2C Zhang G%2C Ding W%2C Duan L%2C Yang J%2C Kui L%2C Cheng X%2C Ruan J%2C Fan W %282018%29 Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches%2E Nature Communications&dopt=abstract


https://scholar.google.com/scholar?as_q=Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Liu&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Lussier F%2DX%2C Colatriano D%2C Wiltshire Z%2C Page JE%2C Martin VJ %282012%29 Engineering microbes for plant polyketide biosynthesis%2E Computational and structural biotechnology journal 3%3A e&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Lussier&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering microbes for plant polyketide biosynthesis.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering microbes for plant polyketide biosynthesis.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Lussier&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Luttik M%2C Vuralhan Z%2C Suir E%2C Braus G%2C Pronk J%2C Daran J %282008%29 Alleviation of feedback inhibition in Saccharomyces cerevisiae aromatic amino acid biosynthesis%3A quantification of metabolic impact%2E Metabolic engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Luttik&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Alleviation of feedback inhibition in Saccharomyces cerevisiae aromatic amino acid biosynthesis: quantification of metabolic impact&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Alleviation of feedback inhibition in Saccharomyces cerevisiae aromatic amino acid biosynthesis: quantification of metabolic impact&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Luttik&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Martin VJ%2C Pitera DJ%2C Withers ST%2C Newman JD%2C Keasling JD %282003%29 Engineering a mevalonate pathway in Escherichia coli for production of terpenoids%2E Nature biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Martin&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering a mevalonate pathway in Escherichia coli for production of terpenoids&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering a mevalonate pathway in Escherichia coli for production of terpenoids&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Martin&as_ylo=2003&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Matasci N%2C Hung L%2DH%2C Yan Z%2C Carpenter EJ%2C Wickett NJ%2C Mirarab S%2C Nguyen N%2C Warnow T%2C Ayyampalayam S%2C Barker M %282014%29 Data access for the 1%2C000 Plants %281KP%29 project%2E GigaScience&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Matasci&hl=en&c2coff=1


https://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Matasci&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Matsumura E%2C Nakagawa A%2C Tomabechi Y%2C Ikushiro S%2C Sakaki T%2C Katayama T%2C Yamamoto K%2C Kumagai H%2C Sato F%2C Minami H %282018%29 Microbial production of novel sulphated alkaloids for drug discovery%2E Scientific Reports&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Matsumura&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Microbial production of novel sulphated alkaloids for drug discovery.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Microbial production of novel sulphated alkaloids for drug discovery.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Matsumura&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Meadows AL%2C Hawkins KM%2C Tsegaye Y%2C Antipov E%2C Kim Y%2C Raetz L%2C Dahl RH%2C Tai A%2C Mahatdejkul%2DMeadows T%2C Xu L %282016%29 Rewriting yeast central carbon metabolism for industrial isoprenoid production%2E Nature&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Meadows&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Rewriting yeast central carbon metabolism for industrial isoprenoid production&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Rewriting yeast central carbon metabolism for industrial isoprenoid production&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Meadows&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Mendez�?�Perez D%2C Alonso�?�Gutierrez J%2C Hu Q%2C Molinas M%2C Baidoo EE%2C Wang G%2C Chan LJ%2C Adams PD%2C Petzold CJ%2C Keasling JD %282017%29 Production of jet fuel precursor monoterpenoids from engineered Escherichia coli%2E Biotechnology and Bioengineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Mendezâ�?�Perez&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Production of jet fuel precursor monoterpenoids from engineered Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Production of jet fuel precursor monoterpenoids from engineered Escherichia coli&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Mendezâ�?�Perez&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Meunier B%2C de Visser SP%2C Shaik S %282004%29 Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes%2E Chemical Reviews&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Meunier&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Meunier&as_ylo=2004&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Miettinen K%2C Dong L%2C Navrot N%2C Schneider T%2C Burlat V%2C Pollier J%2C Woittiez L%2C van der Krol S%2C Lugan R%2C Ilc T %282014%29 The seco%2Diridoid pathway from Catharanthus roseus%2E Nature communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Miettinen&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=The seco-iridoid pathway from Catharanthus roseus.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=The seco-iridoid pathway from Catharanthus roseus.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Miettinen&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Morris JS%2C Groves RA%2C Hagel JM%2C Facchini PJ %282018%29 An N%2Dmethyltransferase from Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine enables microbial phenylalkylamine production%2E Journal of Biological Chemistry%3A jbc%2E RA&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Morris&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=An N-methyltransferase from Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine enables microbial phenylalkylamine production.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=An N-methyltransferase from Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine enables microbial phenylalkylamine production.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Morris&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Munro AW%2C Leys DG%2C McLean KJ%2C Marshall KR%2C Ost TW%2C Daff S%2C Miles CS%2C Chapman SK%2C Lysek DA%2C Moser CC %282002%29 P450 BM3%3A the very model of a modern flavocytochrome%2E Trends in Biochemical Sciences&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Munro&hl=en&c2coff=1


https://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Munro&as_ylo=2002&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Nakagawa A%2C Matsumura E%2C Koyanagi T%2C Katayama T%2C Kawano N%2C Yoshimatsu K%2C Yamamoto K%2C Kumagai H%2C Sato F%2C Minami H %282016%29 Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli%2E Nature communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Nakagawa&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Nakagawa&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Nakagawa A%2C Matsuzaki C%2C Matsumura E%2C Koyanagi T%2C Katayama T%2C Yamamoto K%2C Sato F%2C Kumagai H%2C Minami H %282014%29 %28R%2C S%29%2Dtetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli%2E Scientific reports&dopt=abstract


https://scholar.google.com/scholar?as_q=(R, S)-tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=(R, S)-tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Nakagawa&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1


plant alkaloids. Nature Communications 2: 326Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Narcross L, Bourgeois L, Fossati E, Burton E, Martin VJ (2016) Mining enzyme diversity of transcriptome libraries through DNAsynthesis for benzylisoquinoline alkaloid pathway optimization in yeast. ACS synthetic biology 5: 1505-1518


Narcross L, Fossati E, Bourgeois L, Dueber JE, Martin VJ (2016) Microbial factories for the production of benzylisoquinoline alkaloids.Trends in biotechnology 34: 228-241


Nielsen J, Keasling JD (2016) Engineering cellular metabolism. Cell 164: 1185-1197Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Nishihachijo M, Hirai Y, Kawano S, Nishiyama A, Minami H, Katayama T, Yasohara Y, Sato F, Kumagai H (2014) Asymmetric synthesis oftetrahydroisoquinolines by enzymatic Pictet–Spengler reaction. Bioscience, Biotechnology, and Biochemistry 78: 701-707


Ounaroon A, Decker G, Schmidt J, Lottspeich F, Kutchan TM (2003) (R, S)-Reticuline 7-O-methyltransferase and (R, S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum–cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis inopium poppy. The Plant Journal 36: 808-819


Özaydın B, Burd H, Lee TS, Keasling JD (2013) Carotenoid-based phenotypic screen of the yeast deletion collection reveals newgenes with roles in isoprenoid production. Metabolic Engineering 15: 174-183


Paddon CJ, Westfall PJ, Pitera D, Benjamin K, Fisher K, McPhee D, Leavell M, Tai A, Main A, Eng D (2013) High-level semi-syntheticproduction of the potent antimalarial artemisinin. Nature 496: 528-532


Patnaik R, Zolandz RR, Green DA, Kraynie DF (2008) L-Tyrosine production by recombinant Escherichia coli: Fermentation optimizationand recovery. Biotechnology and bioengineering 99: 741-752


Peralta-Yahya PP, Ouellet M, Chan R, Mukhopadhyay A, Keasling JD, Lee TS (2011) Identification and microbial production of aterpene-based advanced biofuel. Nature Communications 2: 483


Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions.Nature Methods 8: 785


Porter TD (2002) The roles of cytochrome b5 in cytochrome P450 reactions. Journal of Biochemical and Molecular Toxicology 16: 311-316


Preisig-Müller R, Schwekendiek A, Brehm I, Reif H-J, Kindl H (1999) Characterization of a pine multigene family containing elicitor-responsive stilbene synthase genes. Plant Molecular Biology 39: 221-229


Qu Y, Easson ML, Froese J, Simionescu R, Hudlicky T, De Luca V (2015) Completion of the seven-step pathway from tabersonine to theanticancer drug precursor vindoline and its assembly in yeast. Proceedings of the National Academy of Sciences 112: 6224-6229


Reider Apel A, d'Espaux L, Wehrs M, Sachs D, Li RA, Tong GJ, Garber M, Nnadi O, Zhuang W, Hillson NJ (2016) A Cas9-based toolkit toprogram gene expression in Saccharomyces cerevisiae. Nucleic Acids Research 45: 496-508


Rodriguez A, Kildegaard KR, Li M, Borodina I, Nielsen J (2015) Establishment of a yeast platform strain for production of p-coumaric www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from Copyright © 2019 American Society of Plant Biologists. All rights reserved.

https://www.ncbi.nlm.nih.gov/pubmed?term=Nakagawa A%2C Minami H%2C Kim J%2DS%2C Koyanagi T%2C Katayama T%2C Sato F%2C Kumagai H %282011%29 A bacterial platform for fermentative production of plant alkaloids%2E Nature Communications&dopt=abstract


https://scholar.google.com/scholar?as_q=A bacterial platform for fermentative production of plant alkaloids.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=A bacterial platform for fermentative production of plant alkaloids.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Nakagawa&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Narcross L%2C Bourgeois L%2C Fossati E%2C Burton E%2C Martin VJ %282016%29 Mining enzyme diversity of transcriptome libraries through DNA synthesis for benzylisoquinoline alkaloid pathway optimization in yeast%2E ACS synthetic biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Narcross&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Mining enzyme diversity of transcriptome libraries through DNA synthesis for benzylisoquinoline alkaloid pathway optimization in yeast&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Mining enzyme diversity of transcriptome libraries through DNA synthesis for benzylisoquinoline alkaloid pathway optimization in yeast&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Narcross&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Narcross L%2C Fossati E%2C Bourgeois L%2C Dueber JE%2C Martin VJ %282016%29 Microbial factories for the production of benzylisoquinoline alkaloids%2E Trends in biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Narcross&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Microbial factories for the production of benzylisoquinoline alkaloids&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Microbial factories for the production of benzylisoquinoline alkaloids&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Narcross&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Nielsen J%2C Keasling JD %282016%29 Engineering cellular metabolism%2E Cell&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Nielsen&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering cellular metabolism&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering cellular metabolism&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Nielsen&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Nishihachijo M%2C Hirai Y%2C Kawano S%2C Nishiyama A%2C Minami H%2C Katayama T%2C Yasohara Y%2C Sato F%2C Kumagai H %282014%29 Asymmetric synthesis of tetrahydroisoquinolines by enzymatic Pictet%26%23x2013%3BSpengler reaction%2E Bioscience%2C Biotechnology%2C and Biochemistry&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Nishihachijo&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Asymmetric synthesis of tetrahydroisoquinolines by enzymatic Pictet?Spengler reaction&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Asymmetric synthesis of tetrahydroisoquinolines by enzymatic Pictet?Spengler reaction&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Nishihachijo&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Ounaroon A%2C Decker G%2C Schmidt J%2C Lottspeich F%2C Kutchan TM %282003%29 %28R%2C S%29%2DReticuline 7%2DO%2Dmethyltransferase and %28R%2C S%29%2Dnorcoclaurine 6%2DO%2Dmethyltransferase of Papaver somniferum%26%23x2013%3BcDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy%2E The Plant Journal&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ounaroon&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=(R, S)-Reticuline 7-O-methyltransferase and (R, S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum?cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=(R, S)-Reticuline 7-O-methyltransferase and (R, S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum?cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ounaroon&as_ylo=2003&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=�?zaydın B%2C Burd H%2C Lee TS%2C Keasling JD %282013%29 Carotenoid%2Dbased phenotypic screen of the yeast deletion collection reveals new genes with roles in isoprenoid production%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=�?�?zayd�?±n&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Carotenoid-based phenotypic screen of the yeast deletion collection reveals new genes with roles in isoprenoid production&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Carotenoid-based phenotypic screen of the yeast deletion collection reveals new genes with roles in isoprenoid production&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=�?�?zayd�?±n&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Paddon CJ%2C Westfall PJ%2C Pitera D%2C Benjamin K%2C Fisher K%2C McPhee D%2C Leavell M%2C Tai A%2C Main A%2C Eng D %282013%29 High%2Dlevel semi%2Dsynthetic production of the potent antimalarial artemisinin%2E Nature&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Paddon&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=High-level semi-synthetic production of the potent antimalarial artemisinin&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=High-level semi-synthetic production of the potent antimalarial artemisinin&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Paddon&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Patnaik R%2C Zolandz RR%2C Green DA%2C Kraynie DF %282008%29 L%2DTyrosine production by recombinant Escherichia coli%3A Fermentation optimization and recovery%2E Biotechnology and bioengineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Patnaik&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=L-Tyrosine production by recombinant Escherichia coli: Fermentation optimization and recovery&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=L-Tyrosine production by recombinant Escherichia coli: Fermentation optimization and recovery&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Patnaik&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Peralta%2DYahya PP%2C Ouellet M%2C Chan R%2C Mukhopadhyay A%2C Keasling JD%2C Lee TS %282011%29 Identification and microbial production of a terpene%2Dbased advanced biofuel%2E Nature Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Peralta-Yahya&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Identification and microbial production of a terpene-based advanced biofuel.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Identification and microbial production of a terpene-based advanced biofuel.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Peralta-Yahya&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Petersen TN%2C Brunak S%2C von Heijne G%2C Nielsen H %282011%29 SignalP 4%2E0%3A discriminating signal peptides from transmembrane regions%2E Nature Methods&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Petersen&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=SignalP 4.0: discriminating signal peptides from transmembrane regions.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=SignalP 4.0: discriminating signal peptides from transmembrane regions.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Petersen&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Porter TD %282002%29 The roles of cytochrome b5 in cytochrome P450 reactions%2E Journal of Biochemical and Molecular Toxicology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Porter&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=The roles of cytochrome b5 in cytochrome P450 reactions&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=The roles of cytochrome b5 in cytochrome P450 reactions&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Porter&as_ylo=2002&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Preisig%2DM�ller R%2C Schwekendiek A%2C Brehm I%2C Reif H%2DJ%2C Kindl H %281999%29 Characterization of a pine multigene family containing elicitor%2Dresponsive stilbene synthase genes%2E Plant Molecular Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Preisig-Müller&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Characterization of a pine multigene family containing elicitor-responsive stilbene synthase genes&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Characterization of a pine multigene family containing elicitor-responsive stilbene synthase genes&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Preisig-Müller&as_ylo=1999&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Qu Y%2C Easson ML%2C Froese J%2C Simionescu R%2C Hudlicky T%2C De Luca V %282015%29 Completion of the seven%2Dstep pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast%2E Proceedings of the National Academy of Sciences&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Qu&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Qu&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Reider Apel A%2C d%27Espaux L%2C Wehrs M%2C Sachs D%2C Li RA%2C Tong GJ%2C Garber M%2C Nnadi O%2C Zhuang W%2C Hillson NJ %282016%29 A Cas9%2Dbased toolkit to program gene expression in Saccharomyces cerevisiae%2E Nucleic Acids Research&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Reider&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Reider&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1


acid through metabolic engineering of aromatic amino acid biosynthesis. Metabolic Engineering 31: 181-188Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Rodriguez A, Strucko T, Stahlhut SG, Kristensen M, Svenssen DK, Forster J, Nielsen J, Borodina I (2017) Metabolic engineering ofyeast for fermentative production of flavonoids. Bioresource Technology 245: 1645-1654


Rodriguez S, Denby CM, Vu Tv, Baidoo EE, Wang G, Keasling JD (2016) ATP citrate lyase mediated cytosolic acetyl-CoA biosynthesisincreases mevalonate production in Saccharomyces cerevisiae. Microbial cell factories 15: 1


Ryan OW, Skerker JM, Maurer MJ, Li X, Tsai JC, Poddar S, Lee ME, DeLoache W, Dueber JE, Arkin AP (2014) Selection of chromosomalDNA libraries using a multiplex CRISPR system. Elife 3: e03703


Saunders LP, Bowman MJ, Mertens JA, Da Silva NA, Hector RE (2015) Triacetic acid lactone production in industrial Saccharomycesyeast strains. Journal of Industrial Microbiology & Biotechnology 42: 711-721


Schadeweg V, Boles E (2016) n-Butanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A andcytosolic acetyl-CoA. Biotechnology for biofuels 9: 44


Shi S, Chen Y, Siewers V, Nielsen J (2014) Improving production of malonyl coenzyme A-derived metabolites by abolishing Snf1-dependent regulation of Acc1. MBio 5: e01130-01114


Strijbis K, Distel B (2010) Intracellular acetyl unit transport in fungal carbon metabolism. Eukaryotic Cell 9: 1809-1815Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Strucko T, Magdenoska O, Mortensen UH (2015) Benchmarking two commonly used Saccharomyces cerevisiae strains forheterologous vanillin-β-glucoside production. Metabolic Engineering Communications 2: 99-108


Sun T, Miao L, Li Q, Dai G, Lu F, Liu T, Zhang X, Ma Y (2014) Production of lycopene by metabolically-engineered Escherichia coli.Biotechnology Letters 36: 1515-1522


Takemura M, Tanaka R, Misawa N (2017) Pathway engineering for the production of β-amyrin and cycloartenol in Escherichia coli-amethod to biosynthesize plant-derived triterpene skeletons in E. coli. Applied Microbiology and Biotechnology 101: 6615-6625


Tatsis EC, O'Connor SE (2016) New developments in engineering plant metabolic pathways. Current Opinion in Biotechnology 42: 126-132


Tippmann S, Scalcinati G, Siewers V, Nielsen J (2016) Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed. Biotechnology and Bioengineering 113: 72-81


Trantas E, Panopoulos N, Ververidis F (2009) Metabolic engineering of the complete pathway leading to heterologous biosynthesis ofvarious flavonoids and stilbenoids in Saccharomyces cerevisiae. Metabolic Engineering 11: 355-366


Tsuruta H, Paddon CJ, Eng D, Lenihan JR, Horning T, Anthony LC, Regentin R, Keasling JD, Renninger NS, Newman JD (2009) High-level production of amorpha-4, 11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS One 4: e4489


van Rossum HM, Kozak BU, Pronk JT, van Maris AJ (2016) Engineering cytosolic acetyl-coenzyme A supply in Saccharomycescerevisiae: pathway stoichiometry, free-energy conservation and redox-cofactor balancing. Metabolic Engineering 36: 99-115 www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from


https://www.ncbi.nlm.nih.gov/pubmed?term=Rodriguez A%2C Kildegaard KR%2C Li M%2C Borodina I%2C Nielsen J %282015%29 Establishment of a yeast platform strain for production of p%2Dcoumaric acid through metabolic engineering of aromatic amino acid biosynthesis%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Rodriguez&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Rodriguez&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Rodriguez A%2C Strucko T%2C Stahlhut SG%2C Kristensen M%2C Svenssen DK%2C Forster J%2C Nielsen J%2C Borodina I %282017%29 Metabolic engineering of yeast for fermentative production of flavonoids%2E Bioresource Technology&dopt=abstract


https://scholar.google.com/scholar?as_q=Metabolic engineering of yeast for fermentative production of flavonoids&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of yeast for fermentative production of flavonoids&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Rodriguez&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Rodriguez S%2C Denby CM%2C Vu Tv%2C Baidoo EE%2C Wang G%2C Keasling JD %282016%29 ATP citrate lyase mediated cytosolic acetyl%2DCoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae%2E Microbial cell factories&dopt=abstract


https://scholar.google.com/scholar?as_q=ATP citrate lyase mediated cytosolic acetyl-CoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=ATP citrate lyase mediated cytosolic acetyl-CoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Rodriguez&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Ryan OW%2C Skerker JM%2C Maurer MJ%2C Li X%2C Tsai JC%2C Poddar S%2C Lee ME%2C DeLoache W%2C Dueber JE%2C Arkin AP %282014%29 Selection of chromosomal DNA libraries using a multiplex CRISPR system%2E Elife 3%3A e&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Ryan&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Selection of chromosomal DNA libraries using a multiplex CRISPR system.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Selection of chromosomal DNA libraries using a multiplex CRISPR system.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Ryan&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Saunders LP%2C Bowman MJ%2C Mertens JA%2C Da Silva NA%2C Hector RE %282015%29 Triacetic acid lactone production in industrial Saccharomyces yeast strains%2E Journal of Industrial Microbiology %26 Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Saunders&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Triacetic acid lactone production in industrial Saccharomyces yeast strains&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Triacetic acid lactone production in industrial Saccharomyces yeast strains&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Saunders&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Schadeweg V%2C Boles E %282016%29 n%2DButanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A and cytosolic acetyl%2DCoA%2E Biotechnology for biofuels&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Schadeweg&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=n-Butanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A and cytosolic acetyl-CoA.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=n-Butanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A and cytosolic acetyl-CoA.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Schadeweg&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Shi S%2C Chen Y%2C Siewers V%2C Nielsen J %282014%29 Improving production of malonyl coenzyme A%2Dderived metabolites by abolishing Snf1%2Ddependent regulation of Acc1%2E MBio 5%3A e&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Shi&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Improving production of malonyl coenzyme A-derived metabolites by abolishing Snf1-dependent regulation of Acc1&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Improving production of malonyl coenzyme A-derived metabolites by abolishing Snf1-dependent regulation of Acc1&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Shi&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Strijbis K%2C Distel B %282010%29 Intracellular acetyl unit transport in fungal carbon metabolism%2E Eukaryotic Cell&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Strijbis&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Intracellular acetyl unit transport in fungal carbon metabolism&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Intracellular acetyl unit transport in fungal carbon metabolism&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Strijbis&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Strucko T%2C Magdenoska O%2C Mortensen UH %282015%29 Benchmarking two commonly used Saccharomyces cerevisiae strains for heterologous vanillin%2Dβ%2Dglucoside production%2E Metabolic Engineering Communications&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Strucko&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Benchmarking two commonly used Saccharomyces cerevisiae strains for heterologous vanillin-�?²-glucoside production&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Benchmarking two commonly used Saccharomyces cerevisiae strains for heterologous vanillin-�?²-glucoside production&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Strucko&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Sun T%2C Miao L%2C Li Q%2C Dai G%2C Lu F%2C Liu T%2C Zhang X%2C Ma Y %282014%29 Production of lycopene by metabolically%2Dengineered Escherichia coli%2E Biotechnology Letters&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Sun&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Production of lycopene by metabolically-engineered Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Production of lycopene by metabolically-engineered Escherichia coli&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Sun&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Takemura M%2C Tanaka R%2C Misawa N %282017%29 Pathway engineering for the production of β%2Damyrin and cycloartenol in Escherichia coli%2Da method to biosynthesize plant%2Dderived triterpene skeletons in E%2E coli%2E Applied Microbiology and Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Takemura&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Pathway engineering for the production of �?²-amyrin and cycloartenol in Escherichia coli-a method to biosynthesize plant-derived triterpene skeletons in E&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Pathway engineering for the production of �?²-amyrin and cycloartenol in Escherichia coli-a method to biosynthesize plant-derived triterpene skeletons in E&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Takemura&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Tatsis EC%2C O%27Connor SE %282016%29 New developments in engineering plant metabolic pathways%2E Current Opinion in Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Tatsis&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=New developments in engineering plant metabolic pathways&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=New developments in engineering plant metabolic pathways&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Tatsis&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Tippmann S%2C Scalcinati G%2C Siewers V%2C Nielsen J %282016%29 Production of farnesene and santalene by Saccharomyces cerevisiae using fed%2Dbatch cultivations with RQ%2Dcontrolled feed%2E Biotechnology and Bioengineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Tippmann&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Tippmann&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Trantas E%2C Panopoulos N%2C Ververidis F %282009%29 Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Trantas&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Trantas&as_ylo=2009&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Tsuruta H%2C Paddon CJ%2C Eng D%2C Lenihan JR%2C Horning T%2C Anthony LC%2C Regentin R%2C Keasling JD%2C Renninger NS%2C Newman JD %282009%29 High%2Dlevel production of amorpha%2D4%2C 11%2Ddiene%2C a precursor of the antimalarial agent artemisinin%2C in Escherichia coli%2E PLoS One 4%3A e&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Tsuruta&hl=en&c2coff=1


https://scholar.google.com/scholar?as_q=&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Tsuruta&as_ylo=2009&as_allsubj=all&hl=en&c2coff=1



Vickery CR, La Clair JJ, Burkart MD, Noel JP (2016) Harvesting the biosynthetic machineries that cultivate a variety of indispensableplant natural products. Current Opinion in Chemical Biology 31: 66-73


Vogt T (2010) Phenylpropanoid biosynthesis. Molecular plant 3: 2-20Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Wang Q, Xu J, Sun Z, Luan Y, Li Y, Wang J, Liang Q, Qi Q (2018) Engineering an in vivo EP-bifido pathway in Escherichia coli for high-yield acetyl-CoA generation with low CO2 emission. Metabolic Engineering (in press)


Wang R-z, Pan C-h, Wang Y, Xiao W-h, Yuan Y-j (2016) Design and construction of high β-carotene producing Saccharomycescerevisiae. China Biotechnology 36: 83-91


Wang S, Zhang S, Xiao A, Rasmussen M, Skidmore C, Zhan J (2015) Metabolic engineering of Escherichia coli for the biosynthesis ofvarious phenylpropanoid derivatives. Metabolic Engineering 29: 153-159


Watts KT, Lee PC, Schmidt-Dannert C (2006) Biosynthesis of plant-specific stilbene polyketides in metabolically engineeredEscherichia coli. BMC Biotechnology 6: 22


Westfall PJ, Pitera DJ, Lenihan JR, Eng D, Woolard FX, Regentin R, Horning T, Tsuruta H, Melis DJ, Owens A (2012) Production ofamorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proceedings ofthe National Academy of Sciences 109: E111-E118


Williams DC, McGarvey DJ, Katahira EJ, Croteau R (1998) Truncation of limonene synthase preprotein provides a fully active'pseudomature'form of this monoterpene cyclase and reveals the function of the amino-terminal arginine pair. Biochemistry 37: 12213-12220


Willrodt C, David C, Cornelissen S, Bühler B, Julsing MK, Schmid A (2014) Engineering the productivity of recombinant Escherichiacoli for limonene formation from glycerol in minimal media. Biotechnology journal 9: 1000-1012


Wilson SA, Roberts SC (2014) Metabolic engineering approaches for production of biochemicals in food and medicinal plants. CurrentOpinion in Biotechnology 26: 174-182


Winzer T, Kern M, King AJ, Larson TR, Teodor RI, Donninger SL, Li Y, Dowle AA, Cartwright J, Bates R (2015) Morphinan biosynthesisin opium poppy requires a P450-oxidoreductase fusion protein. Science 349: 309-312


Wong J, de Rond T, d'Espaux L, van der Horst C, Dev I, Rios-Solis L, Kirby J, Scheller H, Keasling J (2018) High-titer production oflathyrane diterpenoids from sugar by engineered Saccharomyces cerevisiae. Metabolic Engineering 45: 142-148


Wriessnegger T, Augustin P, Engleder M, Leitner E, Müller M, Kaluzna I, Schürmann M, Mink D, Zellnig G, Schwab H (2014) Productionof the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris. Metabolic Engineering 24: 18-29


Wu J, Zhang X, Dong M, Zhou J (2016) Stepwise modular pathway engineering of Escherichia coli for efficient one-step production of(2S)-pinocembrin. Journal of Biotechnology 231: 183-192


Wu J, Zhang X, Zhou J, Dong M (2016) Efficient biosynthesis of (2S)-pinocembrin from D-glucose by integrating engineering central www.plantphysiol.orgon March 21, 2020 - Published by Downloaded from Copyright © 2019 American Society of Plant Biologists. All rights reserved.

https://www.ncbi.nlm.nih.gov/pubmed?term=van Rossum HM%2C Kozak BU%2C Pronk JT%2C van Maris AJ %282016%29 Engineering cytosolic acetyl%2Dcoenzyme A supply in Saccharomyces cerevisiae%3A pathway stoichiometry%2C free%2Denergy conservation and redox%2Dcofactor balancing%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=van&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: pathway stoichiometry, free-energy conservation and redox-cofactor balancing&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: pathway stoichiometry, free-energy conservation and redox-cofactor balancing&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=van&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Vickery CR%2C La Clair JJ%2C Burkart MD%2C Noel JP %282016%29 Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products%2E Current Opinion in Chemical Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Vickery&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Vickery&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Vogt T %282010%29 Phenylpropanoid biosynthesis%2E Molecular plant&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Vogt&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Phenylpropanoid biosynthesis&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Phenylpropanoid biosynthesis&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Vogt&as_ylo=2010&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wang Q%2C Xu J%2C Sun Z%2C Luan Y%2C Li Y%2C Wang J%2C Liang Q%2C Qi Q %282018%29 Engineering an in vivo EP%2Dbifido pathway in Escherichia coli for high%2Dyield acetyl%2DCoA generation with low CO2 emission%2E Metabolic Engineering %28in press&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wang&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering an in vivo EP-bifido pathway in Escherichia coli for high-yield acetyl-CoA generation with low CO2 emission.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering an in vivo EP-bifido pathway in Escherichia coli for high-yield acetyl-CoA generation with low CO2 emission.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wang&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wang R%2Dz%2C Pan C%2Dh%2C Wang Y%2C Xiao W%2Dh%2C Yuan Y%2Dj %282016%29 Design and construction of high β%2Dcarotene producing Saccharomyces cerevisiae%2E China Biotechnology&dopt=abstract


https://scholar.google.com/scholar?as_q=Design and construction of high �?²-carotene producing Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Design and construction of high �?²-carotene producing Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wang&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wang S%2C Zhang S%2C Xiao A%2C Rasmussen M%2C Skidmore C%2C Zhan J %282015%29 Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives%2E Metabolic Engineering&dopt=abstract


https://scholar.google.com/scholar?as_q=Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wang&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Watts KT%2C Lee PC%2C Schmidt%2DDannert C %282006%29 Biosynthesis of plant%2Dspecific stilbene polyketides in metabolically engineered Escherichia coli%2E BMC Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Watts&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of plant-specific stilbene polyketides in metabolically engineered Escherichia coli.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of plant-specific stilbene polyketides in metabolically engineered Escherichia coli.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Watts&as_ylo=2006&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Westfall PJ%2C Pitera DJ%2C Lenihan JR%2C Eng D%2C Woolard FX%2C Regentin R%2C Horning T%2C Tsuruta H%2C Melis DJ%2C Owens A %282012%29 Production of amorphadiene in yeast%2C and its conversion to dihydroartemisinic acid%2C precursor to the antimalarial agent artemisinin%2E Proceedings of the National Academy of Sciences 109%3A E111%2DE&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Westfall&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Westfall&as_ylo=2012&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Williams DC%2C McGarvey DJ%2C Katahira EJ%2C Croteau R %281998%29 Truncation of limonene synthase preprotein provides a fully active %27pseudomature%27form of this monoterpene cyclase and reveals the function of the amino%2Dterminal arginine pair%2E Biochemistry&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Williams&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Truncation of limonene synthase preprotein provides a fully active 'pseudomature'form of this monoterpene cyclase and reveals the function of the amino-terminal arginine pair&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Truncation of limonene synthase preprotein provides a fully active 'pseudomature'form of this monoterpene cyclase and reveals the function of the amino-terminal arginine pair&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Williams&as_ylo=1998&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Willrodt C%2C David C%2C Cornelissen S%2C B�hler B%2C Julsing MK%2C Schmid A %282014%29 Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media%2E Biotechnology journal&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Willrodt&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Willrodt&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wilson SA%2C Roberts SC %282014%29 Metabolic engineering approaches for production of biochemicals in food and medicinal plants%2E Current Opinion in Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wilson&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering approaches for production of biochemicals in food and medicinal plants&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering approaches for production of biochemicals in food and medicinal plants&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wilson&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Winzer T%2C Kern M%2C King AJ%2C Larson TR%2C Teodor RI%2C Donninger SL%2C Li Y%2C Dowle AA%2C Cartwright J%2C Bates R %282015%29 Morphinan biosynthesis in opium poppy requires a P450%2Doxidoreductase fusion protein%2E Science&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Winzer&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Winzer&as_ylo=2015&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wong J%2C de Rond T%2C d%27Espaux L%2C van der Horst C%2C Dev I%2C Rios%2DSolis L%2C Kirby J%2C Scheller H%2C Keasling J %282018%29 High%2Dtiter production of lathyrane diterpenoids from sugar by engineered Saccharomyces cerevisiae%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wong&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=High-titer production of lathyrane diterpenoids from sugar by engineered Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=High-titer production of lathyrane diterpenoids from sugar by engineered Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wong&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wriessnegger T%2C Augustin P%2C Engleder M%2C Leitner E%2C M�ller M%2C Kaluzna I%2C Sch�rmann M%2C Mink D%2C Zellnig G%2C Schwab H %282014%29 Production of the sesquiterpenoid %28%2B%29%2Dnootkatone by metabolic engineering of Pichia pastoris%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wriessnegger&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wriessnegger&as_ylo=2014&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wu J%2C Zhang X%2C Dong M%2C Zhou J %282016%29 Stepwise modular pathway engineering of Escherichia coli for efficient one%2Dstep production of %282S%29%2Dpinocembrin%2E Journal of Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Wu&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Stepwise modular pathway engineering of Escherichia coli for efficient one-step production of (2S)-pinocembrin&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Stepwise modular pathway engineering of Escherichia coli for efficient one-step production of (2S)-pinocembrin&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wu&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1


metabolic pathways with a pH-shift control strategy. Bioresource Technology 218: 999-1007Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Wu J, Zhang X, Zhu Y, Tan Q, He J, Dong M (2017) Rational modular design of metabolic network for efficient production of plantpolyphenol pinosylvin. Scientific Reports 7: 1459


Wu S, Chappell J (2008) Metabolic engineering of natural products in plants; tools of the trade and challenges for the future. CurrentOpinion in Biotechnology 19: 145-152


Xiao M, Zhang Y, Chen X, Lee E-J, Barber CJ, Chakrabarty R, Desgagné-Penix I, Haslam TM, Kim Y-B, Liu E (2013) Transcriptomeanalysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest.Journal of Biotechnology 166: 122-134


Xu P, Ranganathan S, Fowler ZL, Maranas CD, Koffas MA (2011) Genome-scale metabolic network modeling results in minimalinterventions that cooperatively force carbon flux towards malonyl-CoA. Metabolic Engineering 13: 578-587


Yamanishi M, Ito Y, Kintaka R, Imamura C, Katahira S, Ikeuchi A, Moriya H, Matsuyama T (2013) A genome-wide activity assessment ofterminator regions in Saccharomyces cerevisiae provides a ″terminatome″ toolbox. ACS Synthetic Biology 2: 337-347


Yan Y, Kohli A, Koffas MA (2005) Biosynthesis of natural flavanones in Saccharomyces cerevisiae. Applied and EnvironmentalMicrobiology 71: 5610-5613


Yang D, Kim WJ, Yoo SM, Choi JH, Ha SH, Lee MH, Lee SY (2018) Repurposing type III polyketide synthase as a malonyl-CoA biosensorfor metabolic engineering in bacteria. Proceedings of the National Academy of Sciences: 201808567


Yang J, Guo L (2014) Biosynthesis of β-carotene in engineered E. coli using the MEP and MVA pathways. Microbial Cell Factories 13:160


Yang J, Li Z, Guo L, Du J, Bae H-J (2016) Biosynthesis of β-caryophyllene, a novel terpene-based high-density biofuel precursor, usingengineered Escherichia coli. Renewable Energy 99: 216-223


Yang J, Nie Q, Ren M, Feng H, Jiang X, Zheng Y, Liu M, Zhang H, Xian M (2013) Metabolic engineering of Escherichia coli for thebiosynthesis of alpha-pinene. Biotechnology for biofuels 6: 60


Yang S-M, Han SH, Kim B-G, Ahn J-H (2014) Production of kaempferol 3-O-rhamnoside from glucose using engineered Escherichiacoli. Journal of Industrial Microbiology & Biotechnology 41: 1311-1318


Yang S-M, Shim GY, Kim B-G, Ahn J-H (2015) Biological synthesis of coumarins in Escherichia coli. Microbial Cell Factories 14: 65Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Yang Y, Lin Y, Li L, Linhardt RJ, Yan Y (2015) Regulating malonyl-CoA metabolism via synthetic antisense RNAs for enhancedbiosynthesis of natural products. Metabolic Engineering 29: 217-226


Yao R, Zhao Y, Liu T, Huang C, Xu S, Sui Z, Luo J, Kong L (2017) Identification and functional characterization of a p-coumaroyl CoA 2′-hydroxylase involved in the biosynthesis of coumarin skeleton from Peucedanum praeruptorum Dunn. Plant Molecular Biology 95: 199-213



https://www.ncbi.nlm.nih.gov/pubmed?term=Wu J%2C Zhang X%2C Zhou J%2C Dong M %282016%29 Efficient biosynthesis of %282S%29%2Dpinocembrin from D%2Dglucose by integrating engineering central metabolic pathways with a pH%2Dshift control strategy%2E Bioresource Technology&dopt=abstract


https://scholar.google.com/scholar?as_q=Efficient biosynthesis of (2S)-pinocembrin from D-glucose by integrating engineering central metabolic pathways with a pH-shift control strategy&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Efficient biosynthesis of (2S)-pinocembrin from D-glucose by integrating engineering central metabolic pathways with a pH-shift control strategy&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wu&as_ylo=2016&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wu J%2C Zhang X%2C Zhu Y%2C Tan Q%2C He J%2C Dong M %282017%29 Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin%2E Scientific Reports&dopt=abstract


https://scholar.google.com/scholar?as_q=Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wu&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Wu S%2C Chappell J %282008%29 Metabolic engineering of natural products in plants%3B tools of the trade and challenges for the future%2E Current Opinion in Biotechnology&dopt=abstract


https://scholar.google.com/scholar?as_q=Metabolic engineering of natural products in plants; tools of the trade and challenges for the future&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Metabolic engineering of natural products in plants; tools of the trade and challenges for the future&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Wu&as_ylo=2008&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Xiao M%2C Zhang Y%2C Chen X%2C Lee E%2DJ%2C Barber CJ%2C Chakrabarty R%2C Desgagn�%2DPenix I%2C Haslam TM%2C Kim Y%2DB%2C Liu E %282013%29 Transcriptome analysis based on next%2Dgeneration sequencing of non%2Dmodel plants producing specialized metabolites of biotechnological interest%2E Journal of Biotechnology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Xiao&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Xiao&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Xu P%2C Ranganathan S%2C Fowler ZL%2C Maranas CD%2C Koffas MA %282011%29 Genome%2Dscale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl%2DCoA%2E Metabolic Engineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Xu&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Genome-scale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl-CoA&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Genome-scale metabolic network modeling results in minimal interventions that cooperatively force carbon flux towards malonyl-CoA&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Xu&as_ylo=2011&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Yamanishi M%2C Ito Y%2C Kintaka R%2C Imamura C%2C Katahira S%2C Ikeuchi A%2C Moriya H%2C Matsuyama T %282013%29 A genome%2Dwide activity assessment of terminator regions in Saccharomyces cerevisiae provides a �?�terminatome�?� toolbox%2E ACS Synthetic Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Yamanishi&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=A genome-wide activity assessment of terminator regions in Saccharomyces cerevisiae provides a â�?³terminatomeâ�?³ toolbox&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=A genome-wide activity assessment of terminator regions in Saccharomyces cerevisiae provides a â�?³terminatomeâ�?³ toolbox&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Yamanishi&as_ylo=2013&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Yan Y%2C Kohli A%2C Koffas MA %282005%29 Biosynthesis of natural flavanones in Saccharomyces cerevisiae%2E Applied and Environmental Microbiology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Yan&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of natural flavanones in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Biosynthesis of natural flavanones in Saccharomyces cerevisiae&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Yan&as_ylo=2005&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Yang D%2C Kim WJ%2C Yoo SM%2C Choi JH%2C Ha SH%2C Lee MH%2C Lee SY %282018%29 Repurposing type III polyketide synthase as a malonyl%2DCoA biosensor for metabolic engineering in bacteria%2E Proceedings of the National Academy of Sciences&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Yang&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria.&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Yang&as_ylo=2018&as_allsubj=all&hl=en&c2coff=1

https://www.ncbi.nlm.nih.gov/pubmed?term=Yang J%2C Guo L %282014%29 Biosynthesis of β%2Dcarotene in engineered E%2E coli using the MEP and MVA pathways%2E Microbial Cell Factories&dopt=abstract


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https://www.ncbi.nlm.nih.gov/pubmed?term=Yang J%2C Li Z%2C Guo L%2C Du J%2C Bae H%2DJ %282016%29 Biosynthesis of β%2Dcaryophyllene%2C a novel terpene%2Dbased high%2Ddensity biofuel precursor%2C using engineered Escherichia coli%2E Renewable Energy&dopt=abstract


https://scholar.google.com/scholar?as_q=Biosynthesis of �?²-caryophyllene, a novel terpene-based high-density biofuel precursor, using engineered Escherichia coli&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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https://www.ncbi.nlm.nih.gov/pubmed?term=Yang J%2C Nie Q%2C Ren M%2C Feng H%2C Jiang X%2C Zheng Y%2C Liu M%2C Zhang H%2C Xian M %282013%29 Metabolic engineering of Escherichia coli for the biosynthesis of alpha%2Dpinene%2E Biotechnology for biofuels&dopt=abstract


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https://scholar.google.com/scholar?as_q=Biological synthesis of coumarins in Escherichia coli.&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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https://www.ncbi.nlm.nih.gov/pubmed?term=Yang Y%2C Lin Y%2C Li L%2C Linhardt RJ%2C Yan Y %282015%29 Regulating malonyl%2DCoA metabolism via synthetic antisense RNAs for enhanced biosynthesis of natural products%2E Metabolic Engineering&dopt=abstract


https://scholar.google.com/scholar?as_q=Regulating malonyl-CoA metabolism via synthetic antisense RNAs for enhanced biosynthesis of natural products&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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https://www.ncbi.nlm.nih.gov/pubmed?term=Yao R%2C Zhao Y%2C Liu T%2C Huang C%2C Xu S%2C Sui Z%2C Luo J%2C Kong L %282017%29 Identification and functional characterization of a p%2Dcoumaroyl CoA 2�?�%2Dhydroxylase involved in the biosynthesis of coumarin skeleton from Peucedanum praeruptorum Dunn%2E Plant Molecular Biology&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Yao&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=Identification and functional characterization of a p-coumaroyl CoA 2â�?²-hydroxylase involved in the biosynthesis of coumarin skeleton from Peucedanum praeruptorum Dunn&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

https://scholar.google.com/scholar?as_q=Identification and functional characterization of a p-coumaroyl CoA 2â�?²-hydroxylase involved in the biosynthesis of coumarin skeleton from Peucedanum praeruptorum Dunn&num=10&btnG=Search+Scholar&as_occt=any&as_sauthors=Yao&as_ylo=2017&as_allsubj=all&hl=en&c2coff=1


You S, Yin Q, Zhang J, Zhang C, Qi W, Gao L, Tao Z, Su R, He Z (2017) Utilization of biodiesel by-product as substrate for high-production of β-farnesene via relatively balanced mevalonate pathway in Escherichia coli. Bioresource Technology 243: 228-236


Yu D, Xu F, Zeng J, Zhan J (2012) Type III polyketide synthases in natural product biosynthesis. IUBMB life 64: 285-295Pubmed: Author and TitleGoogle Scholar: Author Only Title Only Author and Title

Zha W, Rubin-Pitel SB, Shao Z, Zhao H (2009) Improving cellular malonyl-CoA level in Escherichia coli via metabolic engineering.Metabolic Engineering 11: 192-198


Zhang C, Chen X, Lindley ND, Too HP (2018) A "plug‐n‐play" modular metabolic system for the production of apocarotenoids.Biotechnology and Bioengineering 115: 174-183


Zhang C, Liu J, Zhao F, Lu C, Zhao G-R, Lu W (2018) Production of sesquiterpenoid zerumbone from metabolic engineeredSaccharomyces cerevisiae. Metabolic Engineering 49: 28-35


Zhang Y, Dai Z, Krivoruchko A, Chen Y, Siewers V, Nielsen J (2015) Functional pyruvate formate lyase pathway expressed with twodifferent electron donors in Saccharomyces cerevisiae at aerobic growth. FEMS Yeast Research 15


Zhang Y, Li S-Z, Li J, Pan X, Cahoon RE, Jaworski JG, Wang X, Jez JM, Chen F, Yu O (2006) Using unnatural protein fusions toengineer resveratrol biosynthesis in yeast and mammalian cells. Journal of the American Chemical Society 128: 13030-13031


Zhao J, Bao X, Li C, Shen Y, Hou J (2016) Improving monoterpene geraniol production through geranyl diphosphate synthesisregulation in Saccharomyces cerevisiae. Applied Microbiology and Biotechnology 100: 4561-4571


Zhao Y, Liu T, Luo J, Zhang Q, Xu S, Han C, Xu J, Chen M, Chen Y, Kong L (2015) Integration of a decrescent transcriptome andmetabolomics dataset of Peucedanum praeruptorum to investigate the CYP450 and MDR genes involved in coumarins biosynthesisand transport. Frontiers in plant science 6: 996


Zhou K, Qiao K, Edgar S, Stephanopoulos G (2015) Distributing a metabolic pathway among a microbial consortium enhancesproduction of natural products. Nature Biotechnology 33: 377-383


Zhou ML, Shao JR, Tang YX (2009) Production and metabolic engineering of terpenoid indole alkaloids in cell cultures of the medicinalplant Catharanthus roseus (L.) G. Don (Madagascar periwinkle). Biotechnology and Applied Biochemistry 52: 313-323


Zhu M, Wang C, Sun W, Zhou A, Wang Y, Zhang G, Zhou X, Huo Y, Li C (2018) Boosting 11-oxo-β-amyrin and glycyrrhetinic acidsynthesis in Saccharomyces cerevisiae via pairing novel oxidation and reduction system from legume plants. Metabolic Engineering45: 43-50



https://www.ncbi.nlm.nih.gov/pubmed?term=You S%2C Yin Q%2C Zhang J%2C Zhang C%2C Qi W%2C Gao L%2C Tao Z%2C Su R%2C He Z %282017%29 Utilization of biodiesel by%2Dproduct as substrate for high%2Dproduction of β%2Dfarnesene via relatively balanced mevalonate pathway in Escherichia coli%2E Bioresource Technology&dopt=abstract

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https://www.ncbi.nlm.nih.gov/pubmed?term=Yu D%2C Xu F%2C Zeng J%2C Zhan J %282012%29 Type III polyketide synthases in natural product biosynthesis%2E IUBMB life&dopt=abstract

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https://www.ncbi.nlm.nih.gov/pubmed?term=Zha W%2C Rubin%2DPitel SB%2C Shao Z%2C Zhao H %282009%29 Improving cellular malonyl%2DCoA level in Escherichia coli via metabolic engineering%2E Metabolic Engineering&dopt=abstract

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https://www.ncbi.nlm.nih.gov/pubmed?term=Zhang C%2C Chen X%2C Lindley ND%2C Too HP %282018%29 A %22plug�?�n�?�play%22 modular metabolic system for the production of apocarotenoids%2E Biotechnology and Bioengineering&dopt=abstract

https://scholar.google.com/scholar?as_q=&num=10&as_occt=any&as_sauthors=Zhang&hl=en&c2coff=1

https://scholar.google.com/scholar?as_q=A

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https://www.ncbi.nlm.nih.gov/pubmed?term=Zhang Y%2C Dai Z%2C Krivoruchko A%2C Chen Y%2C Siewers V%2C Nielsen J %282015%29 Functional pyruvate formate lyase pathway expressed with two different electron donors in Saccharomyces cerevisiae at aerobic growth%2E FEMS Yeast Research&dopt=abstract


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https://www.ncbi.nlm.nih.gov/pubmed?term=Zhang Y%2C Li S%2DZ%2C Li J%2C Pan X%2C Cahoon RE%2C Jaworski JG%2C Wang X%2C Jez JM%2C Chen F%2C Yu O %282006%29 Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and mammalian cells%2E Journal of the American Chemical Society&dopt=abstract


https://scholar.google.com/scholar?as_q=Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and mammalian cells&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_publication=&as_yhi=&as_allsubj=all&hl=en&lr=&c2coff=1

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https://www.ncbi.nlm.nih.gov/pubmed?term=Zhao J%2C Bao X%2C Li C%2C Shen Y%2C Hou J %282016%29 Improving monoterpene geraniol production through geranyl diphosphate synthesis regulation in Saccharomyces cerevisiae%2E Applied Microbiology and Biotechnology&dopt=abstract

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https://www.ncbi.nlm.nih.gov/pubmed?term=Zhao Y%2C Liu T%2C Luo J%2C Zhang Q%2C Xu S%2C Han C%2C Xu J%2C Chen M%2C Chen Y%2C Kong L %282015%29 Integration of a decrescent transcriptome and metabolomics dataset of Peucedanum praeruptorum to investigate the CYP450 and MDR genes involved in coumarins biosynthesis and transport%2E Frontiers in plant science&dopt=abstract

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https://www.ncbi.nlm.nih.gov/pubmed?term=Zhou ML%2C Shao JR%2C Tang YX %282009%29 Production and metabolic engineering of terpenoid indole alkaloids in cell cultures of the medicinal plant Catharanthus roseus %28L%2E%29 G%2E Don %28Madagascar periwinkle%29%2E Biotechnology and Applied Biochemistry&dopt=abstract

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