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CHEM-705
Biosynthesis of Natural ProductsSet C
February - 2014
2
CHEM-705
Biosynthesis of Natural Products
Set C
Eighth-Twelveth LecturesProf. Dr. Shaheen Faizi
2014
3
ALLAH is He “Who has made perfect every thing he has created.” (32:8)
“Our Lord is He Who gave unto everything its proper form and then guided it to its proper functions.” (20:51)
4
The Biosynthesis of
Shikimate metabolites
5
CO2 O
OH
OH
HO
OH
OH
HOOC O
CCoAS O
HOOCCOOH
O
HOOC COOH
O
H2N N
NH
H
COOH
NH2
POO
OH
OH
OHHO
CO2H
OH
HOOC
NH2
COOH
NH2
CH2N
O
OH
S COOH
H2N
NH2
COOH
COOHHO
NH2COOHHS
NH2
COOH
NH2
COOH
NH2
COOH
NH2
COOHHOOC
NH2
H2N H
NH2
O
OHPO
OH
OH
OH
OHC
PO
OH
HOOC
PO
OH
HOOC OP
hv
D-glucose
glycine
L-serine
L-cysteine
L-valine
L-alanine
L-leucine
L-aspartic acid
L-methionine
L-Lysine
Alkaloids
glucose 6P
Glycolysis
6
3
glyceraldehyde 3-P
33-phosphoglyceric acid
Phosphoenolypruvate (PEP)
pyruvic acid
Acetyl-CoA
Krebs cycle
oxaloacetic acid 2-oxoglutaric acid
L-arginine
Pentose phosphate cycle
erythrose-4P
Shikimic acid
Cinnamic acids
Flavonoids
Lignans,Lignins
Aromatic amino acids
Alkaloids
Terpenes, sterols
Mevalonic acid
Fattyacids, Lipids,Prostaglandins,Thromboxanes,Leukotrienes
L-glutamic acid
L-ornithine
AlkaloidsPrimary Metabolism
Acetic acid
H2O Hexokinase
Aldolase
pyruvate kinase
6
H3CS
NH2
CO2HX CH3 (X = O, N, C)
O
SCoA
O
SCoA
COOH
C C
L MethioninC1
C2acetyl-CoA malonyl-CoA
NH2
COOH
L Phenyldanine
NH2
COOH
L TyrHOC6C3
C6C2
C6C1
L TyrL Phe
C6C2N
N
NH
CO2H
NH2
L Trp
NH
N
Indd. C2NH2N
NH2
COOH
L Orn
N
C4N N
NH2
COOH
L Lys
N
C5N N
HN2
7
Pathway of aromatic amino acid metabolism in palnts and micro-organisms is now universally reffered to as shikimate pathway
Shikimic acid Metabolites
Shikimate pathway
Chorismate (9)
OH
COOH
NH2
COOH
and the folate co-enzymes
NH
NH2
CO2
H
L-tryptophan (12)
NH2H
COOH
+HO
L-tyrosine (11)
NH3H
COOH
+
Alkaloids Indole Alkaloids
10, 11, and 12 are protein--amino acids
Isoprenoid quinone (vitamin K1 and K2) coenzyme Q, plant phenols(cinnamic acids, lignans, lignins, etc.)
L-phenylalanine (10)
8
HO
CO2H
OHOH
HO
3-Dehydroquinate (5)
O
CO2H
OHOH
HO
H
OHOH
PO
CO2
NADH
POCH2 H
HOOH
HO
COOH
OH
OOH
PO CO2
CH2
CO2HH
CO2H
OHO OH
3-Dehydroshikimate (6)
OP CH2
COO
NADPH
HO
COOH
OHOH
HOCO2
OHPOH2C
O
OH
OHOH
HO
CO2H
CO2
CO2OOH
CH2
GlucoseGlycolysis
D-Glucose
(PEP) Phosphoenol pyruvate (2)
(PEP) (2)
Pentose phosphate cycle
PEP (2)stereo specific aldol reaction
2
34
56
2 1
cis elimination
of water
quinic acid
1
27
1,4 conjugate eliminaion
of phosphoric acid
Shikimate 3-phosphate 5-Enolpyruvyl shikimate 3-phosphate (8) Chorismate (9)
protocatechuic acid gallic acid
-2H
Erythrose-4- phospate (1)
Reduction
3'-deoxy-D-arabinohep tulosonic acid 7-phosphate
Shikimate (7)
(PEP)Phosphoenol
Pyruvate (2)
1
3
Phosphorylation 1
2
34
5
6
7
DAHP (3)
9
Shikimic pathway
D-GlucosePOCH2H
HO
OH
O O CH2
CO2
P
Glucose
Glycoly
sis
pentosephosphatecycle
Erythrose 4-phosphate (1)
(1) + (2)DAHP- (3-deoxy-D-arabino-heptulosonic acid, 7-phosphate-syuthetase
HO
CO2
POH2C
OH
OHH
O
1
23
4567
Phosphoenol pyruvate (2)(PEP)
synthetase (Enzyme) Aldol condensation (stereospecific)
P = phosphate = P O
O
O3-deoxy-D-arabinoheptulosonic acid 7-phosphate (3) (DAHP)
Mechanism
Enzyme
O OCH2
OPO2C
Phospoenol pyruvatePEP (2)
si
OH
POH2C
OH
H
O
re
H OH4567
Stereospecific
ReactionAldolcondensation
O O
EnzymeCO2
OP
OH
OH
HO
POCH2
OH
Enzyme
OH
POCH2
OH
OH
CO2
O
1
2 3
456
DAHP (3)
Enzyme
O OH
OP
COOH
Hz
HE si
re
OH
HOH2C(CHOH)2(1)
(2)
+
10
3-Dehydroquinate synthetaseOH
POH2C
OH
OH
CO2O1
23
4567
(NAD+) Nicotinamide adenine dinucleotide(coenzyme for oxidation) O
OH
OH
CO2HO
2
34
5
6
H
H
DAHP (3) 3-Dehdroquinate (5)
3-dehydroquinate dehydrase
(isolated and characterised) O
OH
OH
12
3
4
5
6
3-Dehydroshikimate (6)
CO2
H
Mechanism (5 6) (cis elimination of H2O
HHO
OH
CO2
OH
O
123
45
6 X+NH2
B:(basic gp)
HOH
OH
CO2
OH
N
123
45
6X+
B:Schiff base
3-dehydroquinate (5) (boat or skew boat conformation)
Enzyme (3-dehydroquinate dehydrase)
(electropositive gp)
1234
5
6
+
B
N
OH
CO2
X
HOHO
H+(enolate type anion)
B:
X
CO2
OHN
HO
OH
1
23
4
5
6
+
CO2
OHO
HO1
23
4
5
6
(6) O
OH
OH
CO2
3-Dehydroshikimate (6)
1
Enzyme+
*
Enzyme
11
CO2
OHO
OH3-Dehydro shikimate (6) Shikimate (7)
Isolated in 1885 from aniseed fruit
CO2
OHHO
OH
3-dehydroshikimate reductase (enzyme isolated and characterized)
Shikimate kinase(enzyme isolated and characterized)
(ATP)(NADPH)
CO2
OHPO
OHShikimate 3-phosphate (7)
5-enolpyruvylshikimate 3-phosphate synthetase (enzyme isolated and characterized)
Phosphoenol pyruvate (PEP)
1
54
3
6
CO2
OPO
OH
CO2
CH2
CO2
CH2HO5-Enolpyruvyl shikimate 3-phosphate (8)
Mechanism for the formation of 8
CO2
OHPO
OH
1
54
3
62 H H
CO2PO
CO2
OPO
OH
H H
CO2
OP
CO2
OPO
OH
CO2
4
2
3
1
5
6
HR
HS
(8)
H AEnzyme
Shikimate 3-phosphate (7)P = phosphate
CO2
OPO
OH
H H
CO2
OP
H
1,4 conjugateelimination ofphosphoric acid
chorismate synthetase(enzyme isolated charactered)
O
CH2
HS
CO2
CO2
OH
Chorismrate (9)
(PEP)
12
CO2-
HO
OH
OH
OP
HO
HR
HS
O
CH2
CO2
CO2
X
OP
H+
O
CH2
HS
CO2
CO2
OH
XO
CH2
O2CHO
CO2
HR
Shikimate (7)( Substrate )
Shikimate Kinase
( Enzyme )Complex
This complex was analysed by multinuclear multidimensional NMR spectroscopy. Total assignment of resonances has been made and the assignment data have been deposited in the BIO Mag Res Bank database
Mechanism 8 9
(overall trans stereochemistry of elimination of phosphonic acid)
Enzyme
12
3
4
5
6
5-enolpyruvyl shikimate3-phosphate (8)
Enzyme
1
2
34
5
6
A two-step 'X group mechanism' was postulated in order to account for the overall trans stereochemsitry of the elimiation process
Chorismate(9)
1
2
34
5
+
Enzyme
Nat. Prod. Report 20, 119-136(2003)
PO = Phosphate
13
CO2
OH
O CO2
CH2
CO2
NH2
O CO2
CH2
CO2
NH2
CO2
O
+4 - amino-4- deoxychorismate lyase
( ADCL )
Pyruvate4 - Aminobenzoate(part of folic acid)
Chorismate 4 - Amino-4-deoxychorismate
44
L-Glutamine
amination using ammonia (generated from glutamine as nucleophile)
H2N
O
CO2
NH3
Enzyme
14
COOH
OH
COOH
OH
O CH2
CH2
COOH
NH2
NH
NH3+H
COO
CO2
HNH3
+
HO
CO2
HNH3
+
p-Hydroxybenzoic acid
(13)
p-Aminobenzoic acid(folate coenzyme)
(14)
(12)L-Tryptophan
(11)L-Tryosine
(10)L-PhenylalanineChorismate (9)
Isoprenoid quinones(vitamin K1 & K2, coenzyme Q)
Biosynthesis of the Aromatic Amino-Acids(10, 11)
CO2
OH
O
CH2
CO2
Chorismate(9)
1
2
3
4
5
6
Chorismate
mutase
OH
C
O
O
prephenatedehydratase
CO2
H2O
O
CO2
Trans amination
NH3
CO2
H
4
Prephenate (25)
Phenylpyruvic acid (26)
L-Phenylalanine (10)
chorismatemutase
OCO2
OH
O2C
prephenatedehydrogenase
CO2
O
CO2
Trans amination
NH3
CO2
H
4
Prephenate (25)p-Hydroxyphenylpyruvic acid L-Tyrosine (11)
OCO2
1
2
345
6
H OH OH
15
Rearrangement of chorismic acid to prephenic acid
COOH
OHOH
H
COOH
1
2
34
6
5
Inversion of conformation of ring
OH
COOHO
C
HOOC
H
1
234
5
6
(9a) chair type conformation of interacting system
(9b)
CH2
COOH
O
COOH
1
23
45
6HO
Prephenic acid (25)
chorismate mutaseenzyme
(Ortho-Claisen type rearrangement)
H
CO
CO
O
CO2
OH
Prephenate (25)
16
C
NH2
O
O COOH
NH2
H
CO CO2
H
NH2
C
O
OH
NAD+
oxidation
O
OH
Claisenrearrangement
C
O
OH
CO2H
4-Amino-4-deoxychorismic acid Imine
CO2
O
NH2
CO2H
Transamination
NH2
NH2
CO2H
Hydroxylation
CHCl2CSCoA
O N
NH2
COOH
C
H
C
O
H
ClCl
HO
L-p-Amino phenylalanine(L-PAPA)
N
NO2
CH2OH
C
H
CH
O
ClCl
HO
Reductionofacid
OxidationofNH2
Chloromphenicol(chloromycetin)
PLP N-acylation
PLP =
Pyridoxal 5'-
Phosphate
17
Biosynthesis of Tryptophan
anthranilate synthetase(removed of enolpyruvyl gp as pyruvate
Chorismate (9)
COO
O
HO
CH2
CO2
L-Glutamine
H2N
O
CO2
H NH3+
COO
NH3
Alkaloids
Anthranilate (35)
CO2
NH3
(35)
CH2OP
H
H
PPO
H H
OH OH
O
5-Phosphoriboxylpyrophosphate (36)
Phosphoribosyltransferase
CO2
CH2OP
H
NH
PPO
H H
OH OH
O
(lablie amino sugar)amino aldose
Amadori typerearrangment
NH
HO H CH2OP
OH
H
Enzyme
CO2
NH
O
HO H
CH2OP
H OP
(amino ketose)
DeoxyribuloseAmadoricomound (37)
Indolglycerol phosphate(IGP) (38)
Pyridoxal phosphateL-Tryptophansynthetase(,2)
NH
CO2
NH3
H
L-Tryptophan (12)
CO2HOCH2
HH3N+
N
O
CH2
OH
P
O
HO
Me
CHO
OH
Pyridoxal phosphate coenzyme
1
2 3
4
5
L-Serine
18
Mechanisms
anthranilatesynthetase
Chorismate (9)
CO2
O
HO
CH2
CO2
L-glutamine
H2NC
O
COOH
H2N H
1
234
5
6CO2
O
HO
CH2
C
H
NH2
O
O
HN O
CH2
OHH
CO2
HH
Cyclic intermediate
O
HN O
CH3
OH
CO2
H
COOHHN O
CH3OH2O
H2OCH3 C
O
COH
O
pyruvic acid
COOH
NH2
CO2
NH3+
alkaloids
Anthranilic acid Anthranilate
19
Amadori Rearrangement (The Carbolydrates Chem. & Biochem. Sec. Ed 1980)
OH
OH
H
OHH
OHH
OH
CH2OH
H
D-Glucose
NH2
CH3
+ H2O+H+
OH
OH
H
NHH
OHH
OH
CH2OH
H
heat 30 mint.
CH3
H+
Labile productGlycosyl amine(Amino sugar)
CH3NHH2C
O
HOC
HC OH
CH OH
CH2 OH
Stable product(crystalline)
(Amadori compound)
H
20
O
H H
CH2OP
HPPO
HOH HO
COOH
NH2
NH
CO2
CH2OP
HH
H H
OH HOOH+
H+
NH
CO2
CH2OP
HH
H H
OH HOHO
+N
CO2
CH2OP
HH
H H
OH HOHO
H X
N
CO2
CH2OP
H
OH H
C HOHO
H
H
HX
N
CO2
H
O
HHO
CH2OP
OHH
1
2 3
4
5
5-Phosphoribosyl1-pyrophosphate (36)
+
Anthranilic acid (35)
Phosphoribosyl transferase
1
2 3
4
5
(Amino sugar)(Glycosyl amine)
Amadorirearrangement
+
Immomium compound
Enzyme
Enaminol
Deoxyribulose (37)(Amadori compound)
chorismate(9)
21
Deoxyribulose (37)
CO2
NHHO H
OH
CH2OP
HO NH+
OH
R
OHH
C
O
O
CO2
NH
OH
H
HO H
H
OH
CH2OP
H2O
NH
HO H
H
OH
CH2OPL-tryptophan synthetase , (enzyme)
PyridoxalphosphateL-serine
NH
NH3
CO2
H
Indolglycerolphosphate (IGP) (38)
L-Tryptophan (12)
N
HO
Me
C
O
H
H2C
OP
O
H
OH
Mechanism
L-tryptophan synthetase
Enzyme
NH2Apo-enzyme
Pyridoxal phosphate(co-enzyme)
NH
H2C
HC
N
OH
Imine(Holoenzyme)
Enzyme
O
Me
NH2 R
Serine
HOCH2 CO2
HH2N
Serine
+
NH
Me
OH
HCPO3
O
H2C
N CH
Enzyme
NH2COOH
H2C OH
Imine
H
CH2OP
OHH
O3P
22
NH+
H2C
HC
N
OH
Imine
C
PO3
O
Me
C
HO
OH
H2CHOEnzyme
NH
H2C
HC
N
OH
Imine
C
PO3
O
Me
C
O
H2CHOEnzyme
H+
OH
NH
H2C
HC
N
OH
C
OPO3
Me
C
O
H2C
Enzyme
OH
OH
H2O
(A)
NH
HOH
CH2OP
H
OH
CH2C
N
HC
NH
H2C OH
Me
OPO3
EnzymeC
O
OH
Indolglycerolphosphate (38)(IGP)
(A)
NH
CH2
HOH
CH2OP
H
OH
C
N
C
O
OH
HC
NH
OHO3POCH2
Me
Serine residue
Enzyme
23
NH+
CH2
OH
CH2OP
H
OH
H+
C
N
C
O
OH
HC
NH
OHO3POCH2
Me
Enzyme
NH
CH2 C
N
C
O
OH
C
NH
OHO3POCH2
Me
H
H
OH2
NH
H2CNH2
COOH
H
Serine residue
+
N
HO
CH
CH2
Me
O
O
Pyridoxalphosphate(coenzyme)
+ Enzyme(apo enzyme)
L-Tryptophan(12)
Metabolism in higher organisms and micro-organisms
NH
HO
NH2
5
NH
Indole
Pyruvate + NH3
Plants
Indole Alkaloids
D-glyceraldelyde
CH
O
CHOH
CH2OH
H
Enzyme
Serotinin
P
O
OH
OH
degradation
24
O
HCH2OP
H
OH
NH
HOH2CCO2
H3N+
H+
Indole
NH
H
IGP (38)
subunit of enzyme complex
L-tryptophan synthetaseNH
H
C
O
H
CH2OP
OH
+
not a true intermediate D-glyceraldehyde
2(Sub-unit of enzyme compound)
L-serine
CO2
NH3
H
NH
L-Tryptophan
Isotopic tracer andEnzymatic studies
Pyridoxalphosphate
25
Anthranilate
Aurachin A
(e-transport inhibitors)Nat. Prod. Report 20, 119-136 (2003)
CO2
NH3+
type IIDAHPisozymes
N
O
O
HO
26
Biosynthesis of pyrrolnitrin by bacteria
NO2 NH
Cl
Cl
Pyrrolnitrin (1) is an antifungal tryptophan derived metabolite produced by a number of pseudomonads. It is a phenylpyrrole derivative and has high antibiotic activity against dermatopytic fungi, especially against members of the genus Trichophytonand was soon marketed in Japan under the name PYRO-ACE for the treatment of superficial dermatophytic infections.
A) Feeding experiments and ioslation of intermediates
COOH
NH2
Anthranilic acid (2) DL-phenylalanine (3) Tryptophan (4)
COOH
NH2
NH
COOH
NH21 2
3
4
5
6
7
8
Pyrrolnitrin (1)
Addition of 2 or 3 to Pseudomonas aureofaciens inhibited the production of 1, whereas addition of (4) resulted in an increase of the production of 1. Feeding experiments using DL-tryptophan 3-14C confirmed that 1 is derived from 4.
a) Isolatin of enzymesb) Characterising and cloning of the biosynthetic genec) Sequencing of genes
B) Enzymology and molecular genetics
27
Tryptophan (4)
NH
CO2H
NH2 tryptophan
7-halogenase[O], NADH, FAD
Epoxide(intermediate)
NH
CO2H
NH2
O
Cl-
7-Chlorotryptophan (5)
NH
CO2H
NH2
Cl
H2O
NH
CO2H
NH2
Cl
HO
H
7
7
8
7NH2 N
H
Cl
monodechloro-aminopyrrolnitrin
3-halogenaseCl-, NADH, FAD
NH2 NH
Cl
(6)
(7)
monodechloroaminopyrrolnitrin synthase
Cl
NO2
Cl
NH
Cl
Pyrrolnitrin (1)
Nat. Prod. Report 17, 157 (2000)Nat. Prod. Report 20, 119 (2003)
aminopyrrolnitrin
oxygenase
28
L-TryptophanNH
NH2
CO2H
H
cytochrome P450 enzyme(isolated and characterized)
NH
N OH
Indole-3-acetaldoxime
3
NH
N3
Indole-3-acetonitrile
NH
COOH3
Indole-3-acetic acid(IAA)
NH
NOSO3
S
indolyl-3-methyl glucosinolate
Nat. Prod. Report. 20, 119 (2003)
Glucose
Isothiocyante
29
Biosyn. of m-carboxy-substituted aromatic amino-acids (30-33) (non-protenic)
O
H
OH
CO2
CO2
CH2 +H2O
O
OH
CO2
CO2
CH2
H2O
OH
O
O2C
CO2
OH OH
O
CO2
(28) (9)(25) (27)
Chorismic acidPrephenate
OH
H
CO2
(11)
NH3+
Isochorismic acid
CO2
H
OHH
CO2
O
Adrenaline
L-Tyrosine
OH
H
NHMe
HO
OH
OH
H
CO2
NH3+
HO
CO2
NH3 O2C
H
CO2
NH3 O2C
H
OH
CO2
H3N
CO2
H
(32)
(30)(31)
(34)L-Dopa
CO2
H3N
CO2
H
(33)
OH
NH
O
Omelanin pigment
Alkaloids
3',4'-Dihydroxy L-phenylalanine (non-protein amino acid)
(30-33) These acids are members of a large group of amino acids found in higher plants that are not normally encountered as constituents of proteins
hydroxylase
(29)
n
Ortho Claisen rearrangement
3'4'
30
H
H
R
HO
HO
NH3
COO
H
H
O
H
R
R
O
H
H
NH2
HHO
HO
HO
CO2
H
OH
R
NH2
HO
H
H
OH
NHM
HHO
HO
HO
HO
OH
R
HO
H
R
+
Arene oxide
hydroxylase
L-dopadecarboxylase
*
Aryl hydroxylation and NIH shift
Hydroxylase
NIH shift : J. Nat. Prod. 63, 713 (2000)
L-Tyrosine
Dopamine
dopamine -hydroxylase
L-methionineN-methyltransferase
Adrenaline(catechol amine)
L-Dopa
Oxygen atom type species
*
*
31
Methylation of RNH2 or ROH with methionine
N
N N
N
NH2
O
OH
HO
O H2CPPP
S:H3C
H2C
CH2
HC NH2
COOH
(Mithionine)
N
O
OH
HO
H2C
CH2
CH2
HC NH2
COOH
S-adenosyl methionine(SAM)
S+H3C
R NH2
Transfer of methyl group
N
O
OH
HO
CH2
CH2
CH2
CHNH2
COOH
S-adenosylhomo cysteine
S
(ATP) (Amine)
RNH CH3(Methyl amine)
+
32
HR
NH3H
CO2-
Hs
31
2
L-phenylalanine
L-Phenylalanineamino lyase (PAL)
HR
CO2-
H NH3
( anti elimiation )Trans-Cinnamate( Cinnamic acid )
Metabolism of L-phenylalanine
CO2
HO (Coumarte)
(p-Coumaric acid)
hydroxylase
NIH shift
CO2
HO Caffeate
(Caffeic acid)
HO
CO2
HOFerulate
(Ferulic acid)
hydroxylase
NIH shift
CO2
HOSinapate
(Sinapic acid)
MeOMethionine
SAM (ATP)SAM
Methionine
(ATP)
OMe
COOH
Trans cinnamic acid
COOH
Benzoic acid
COOH
OH
Nat. Prod. Report 173, (1994)
HH
CO2
HNH3
HO Tyrosine
CO2H
HO
COOH
HO
COOH
HO
COOH
HO
HO
Similar proposals have also beenadvanced to account for the biogenesis of related aldelydes, alcohols and the phenylacetic acids.
HO
hydroxylase
NIH shift
H3CO
33
+
H+H
CH2-OHCOOHCOOH
NH2
CH2
-H2O
H
CH3
+
CO2H
OH
H2O COOH
H-O
HO
CH2OH
OH
C
HO
OH
C
OH
OH
O
NAD+
L-Phenylalanine Cinnamic acid
-
Polymerisation
Lignan Lignin
x2 xn
reverse aldol reaction
Eugenol
Enzyme Enzyme Enzyme
Enzyme
Enzyme
Enzyme Enzyme
34
H2N
CO2H
HO
Tyrosine
NH
CO2H
HOOH
Cytochrome P-450
N
H
HO OHN
CO2H
OHHO
4 - Hydroxyphenyl acetaldoxime
N
H
HOHO
HOOCHOOC
C
OGluc
C
HO
N
Triglochinin
Natural Product Report 20, 119 (2003)
4-Hydroxyphenylacetonitrile
C
HO
OH
HO
GlucOH
C
Taxiphylin
N
N N
Enzyme
Enzyme
35
O
MeO
MeO
O
Me
Me
H
Polyprenylside chain
n
5,6-Dimethoxy 3-methyl-2-trans.polyprenyl -1,4-benzoquinones ( Coenzyme Q ) ( n = 1-12 )
Ubiquinones ( Coenzyme Q ) are localized in mitochondria of plants and animals
Me
H
O
O
Me
n
Vatamin K- 1
CO2-
HNH3
O
L-Tyrosine
I
HO
I
I
I
+ COOH
N
O
Me
O
NH2
COOH
Me
L-Tryptophane
Actinocin( antibiotic) (52)
O OH
COOH
OH
OHOPseudopurpurin(anthraquinone)
Lawsone
O
OH
O
Thyroxine
Isoprenoid Quinones
12
35
6
Lipid soluble quinones
36
O
O
OH
BzCNH
O
13
Taxol
COOH
H
HRHs
NH2
3
15
21
Phenylalanineaminomutase
- Phenylalanine
COOH
H
HRHs
NH2
15
- Phenylalanine
Phenylisoserine sidechain of taxol
O
O
OH
13
Nat. Prod. Report 17, 269 (2000)
*
*
BzCNH
O
Enzyme BenzoylationHydroxylation
37
COOH
Cinnamic acid
COOH
OH
O
Coumarin
O
O
O
OMe
Lignans
Pinoresinol Podophyllotoxin
C
O
N
CH3
OCH3
Herclavine
HO
Acetate pathway
PhenolsMeta-Substitutionpattern of OH
Shikimate pathway
Phenolsp-hydroxyo-hydroxy or1,2,3-trihydroxy substitutionpattern of OH
Enzyme
Phytochemistry, 71 1808-1824 (2010)
38
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