1

CHEM-705

Biosynthesis of Natural ProductsSet C

February - 2014

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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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