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GenomaticaSustainable Chemicals
GenomaticaSustainable Chemicals
Genomatica
Pacific Rim SummitDecember 7-9, 2014Mark J. Burk, CTO
Genomatica: Sustainable ChemicalsTechnology Provider to the Chemical Industry
• Exact same chemicals
• Better economics
• Equivalent performance
• Reduced energy use
• Lower carbon footprint
• Feedstock diversification
Regionally
Advantaged
FeedstockBasic & Intermediate
Chemicals
Existing products
sold globally
Tolerance
High titerHigh
yield
High
rate
High Performance
Organisms and Processes
Robust unit
operations
Three Pillars of Bioprocess DevelopmentStrain design guided by process design
Simple BC Fermentor
6.6 m
Tower diameter
T-T
27.4 m
3m
Skirt
Distance
from End
EngineeredCells
Air
Exhaust Gas
SugarsMedia
Purified ChemicalMeet industry specs
Optimize fermentationconditions
Optimize recovery and purification
Optimize sugar to chemical flux
Strain Engineering
to Produce Chemical
Fermentation
DevelopmentRecovery/Purification
PentosePhosphatePathway
Ac-CoA
Gly
coly
sis
Chemical
ChemicalPathway
F6P
G3P
Feedstock
Existing
CentrifugeUltrafiltration
Evaporation
Lights Distillation
Cells/Solids
Water
UF Retentate
Lights
Purified
BDO
Sucrose/
Glucose
Fermentation
Nanofiltration
NF Retentate
Ion Exchange
BDO Distillation
Sterilizer
Residue
Cell Removal Salt/Media Removal
Purification
Dewatering
Water
Hydrogenation
Heavies Removal
Existing Existing
Existing
New
New
Platform Attributes:
Computer-aided design for biology (since 2000)
Enables focused efficient experimentation
Integrated bioprocess design, scale-up, economics
Rapid, cost-effective, lower risk development
Process
Engineering
Predictive
Computer Models
Experimental
Biotechnology Biotechnology
Platform
Advantaged
Process
Technology
Integrated Bioprocess Technology Platform
Confidential
Commercial Strain Engineering Challenges
Commercial scale fermentations introduce unique challenges
Fast growth,
Minimal lag
in prodn
Increase rateImproved enzymes
Lower by-products
Sugar uptake rate
Aeration, co-factor balance
Delay production slowdownNutrient limitation
Osmolarity
Tolerance, stress
Enzyme inhibitionGenetically stable hostFully integrated – no plasmids
Constitutive expression – no IPTG
Commercial conditionsTolerate heterogeneous aeration
Perform at high pCO2 (0.3-0.4 atm)
Complete sugar consumption
Minimal defined mediaLowest cost, ensure cellular
requirements satisfied,
low downstream impact
Titer
(g/L
)
Target
Titer
Time
Sugars
1,4-Butanediol(Biobased BDO)
BDO-producing E. coli
Genomatica technology platform has enabled commercial targets
The GENO BDOTM Process in Engineered E. coli
• 1.4 M ton/year
• PBT, TPU, Spandex
• Direct production from sugars
Improved BDO Process = Lower Production Costs
0
20
40
60
80
100
120
140
0 12 24 36 48 60 72
BD
O T
ite
r (g
/L)
Time (h)
Dec, 2013
Nov, 2012
Apr, 2012
Feb, 2012
May, 2011
Mar, 2011
Jan, 2009
T = 140 g/L
R = >3 g/L/hr
Y* = >102 %
Y* = % of commercialization yield target
E. coli
Glycolysis
TCA
Cycle
BDO
PathwayBDO
E. coli
Sugars Glycolysis
TCA
Cycle
BDO
Pathway
140 g/L
BDO
CO2
Biomass
4HB
Ethanol
Acetate
GABA
Glutamate
Others
Unknown
1,4-BDO
CO2
Biomass
4HB
BDO
CO2
Biomass
4HB
Ethanol
Acetate
GABA
Glutamate
Others
Unknown
1,4-BDO
CO2
Biom.
LowerBy-products
LowerCost
($ / Ton, 50KT Capacity)
($ / lb)
2009 2012 2015 2018 Leading Petro
Technology
Indirect Bio-BDO
TechnologyBDO Price
Historical
Base Case Projection
Upside Case Projection
North America
Europe
Price
Cash Cost
GENO BDOTM Process Commercialization Journey 5 years from concept to commercial production (>4k tons produced & sold)
BDO Producing Organisms – 2008 Purified BDO – 2009 3,000 Liter Piloting – 2010
Commercialization – 2012-13…
600,000 L
Integrated Demo Plant – 2011 Shipping Tons at a Time – 2011
13,000 L
MBI
Tate & Lyle DuPont Tate & Lyle
Robust Scale-Up / Scale-Down of 1,4-BDO ProcessUnderstanding and testing of key scale parameters
Consistent fermentation performance across lab, pilot, demo, and commercial scales
Low variability over 50+ large scale fermentations process robustness and predictability
Robust Performance at Commercial-Scale
0%
20%
40%
60%
80%
100%
120%
0 10 20 30 40 50
Batch No.
Percent Average Commercial Scale IRR'
0%
20%
40%
60%
80%
100%
120%
0 10 20 30 40 50
Batch No.
Percent Average Commercial-Scale Yield
Top 5 Fermentation RunsFermentation Run
Consistent Scale-up to Commercial
13,000L
Demonstration
ScaleCommercial
Scale
~ 50x
scale-up
Commercial vs Demo
Titer 98%
Rate 104%
Yield 100%
Average Fermentation
Performance
( ~50 runs at commercial
scale vs. average demo
scale)
Consistent Performance Across Development Scales
0%
30%
60%
90%
120%
2L 30L 13kL
Tit
er,
g/L
BD
O(a
s %
of 2L)
0%
40%
80%
120%
160%
2L 30L 13kL
Rate
, g
/L.h
r (a
s %
of 2L)
0%
30%
60%
90%
120%
2L 30L 13kL
Yie
ld, g
/g(a
s %
of 2L)
Lessons Along the Way
Biology has a lot to offer – direct conversion of alternative primary feedstocks to chemical products
Commercializing industrial biotechnology for chemicals is not easy:
• Commercializing new-to-the-world technology in a conservative mature industry
• Achieving competitive economics – both organism and process performance are important
• Validating value proposition (ROI) to justify development investment
• Financial committment – it will always take longer and cost more than you think
• Hitting performance guarantees and meeting industry specs
• Chemical industry inexperience with fermentation and Ag feedstocks
Feedstock flexibility is critical – global industry vs regional feedstock advantages
• Conventional sugars – available but volatile prices, food vs chemicals, low cost limited to US, Brazil, Thailand, India
• Biomass sugars – not ideal for fiber/polymer grade chemicals, sugar quality and cost remain major challenges
• C1 feedstocks – lower cost is attractive, but technically more challenging to engineer strains/processes
Technology platform matters – nature is complex; drive down timelines/resources to achieve comm. perf. targets
Partnerships are key – feedstock, scale-up, engineering, commercial ops, product distribution, marketing, sales...
Innovative Chemical Processes via Biotechnology
Genomatica’s Innovation Center in San Diego, California – over 115 employees
Thanks!
“Innovation distinguishes between a leader and a follower.” Steve Jobs, Apple CEO
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