8.

Shikimates and
Phenylpropanoids
RA Macahig
FM Dayrit
OH

CO2H

O

HO
HO

OH

OH
OH

OH
shikimic acid

O

luteolin

Introduction
Shikimic acid is the key intermediate of a large group
aromatic natural products. The isolation of shikimic acid was
first reported from aniseed (Illicium anisatum) and the fruit of
I. religiosum, whose Japanese name was “shikimi-no-ki” (shi 
four; kimi  seasons; no  of; ki  tree, literally “tree of four
seasons”). Shikimic acid has since been found in many plants,
bacteria, yeasts and moulds.
It is estimated that this group accounts for 35%
CO2H
of plant dry mass, and that one-fifth of the
carbon fixed by plants is channeled to shikimic
acid metabolites, such as the lignins.
Shikimic acid is the precursor of three important
aromatic amino acids: phenylalanine, tyrosine,
and tryptophan.
8.0 Shikimates & phenylpropanoids (Dayrit)

HO

OH

OH
shikimic acid
2

Overview

OP

D-glucose
H
pentose
phosphate
cycle

H+

_
O2C
phosphoenol pyruvate

glycolysis

OH

H

PO

H-O

O
H

O

_
O2C

HO

OH

OH

heptulose

D-erythrose-4-phosphate

Shikimic acid is produced directly
from two D-glucose metabolites:
phosphoenol pyruvate (C3) and Derythrose-4-phosphate (C4) condense
to form the seven carbon heptulose.
Heptulose cyclizes to form 5dehydroquinate which loses water to
form shikimic acid.

H H

_
CO2

O

HO

_
CO2

O

OH

OH
OH

OH

5-dehydroquinate

3-dehydroshikimate

_
CO2

HO

OH
OH
shikimate

8.0 Shikimates & phenylpropanoids (Dayrit)

3

Prephenic acid leads to the phenyl propanoids (C6-C3) and the flavonoids (C6-C3-C6). lignins CO2H phenyl propanoids + (3 x Ac-CoA) phenols OH prephenic acid 8. tryptophan 5 O OH 5-enolpyruvylshikimate -3-phosphate CO2H O CO2H OH chorismic acid EPSPS: 5-enolpyruvyl shikimate-3-phosphate synthase phenylalanine.HOCH2 H HO O H Shikimic acid is converted to 5-enolpyruvylshikimate-3-phosphate. OH OH H H H OH D-glucose CH3 CO2H O CO2H 1 CO2H EPSPS HO OH OH shikimic acid CO2H 3 PO benzoic acids. tyrosine O HO2C lignans.0 Shikimates & phenylpropanoids (Dayrit) flavonoids styrenes benzoic acids 4 . which loses phosphate to yield chorismic acid and prephenic acid. Chorismic acid is the branch point to a group of benzoic acid metabolites and tryptophan. and the amino acids phenylalanine and tyrosine.

n = 4-13 5 .In microorganisms: [O] polyketide aromatic compound quinone In plants: [O] Overview of biosynthesis of quinones. Depending on the organism. quinones can arise via the polyketide or shikimate pathways. Polyketides (Dayrit) O n ubiquinones: R = H. CH3 . polyketide aromatic compound quinone quinone shikimate aromatic compound + terpene [O] quinone (mixed metabolite) quinone from shikimate: OH quinones from shikimate + terpene: OH O OH O H OH CO2H OH homogentisic acid alkarinin O R H 5.

R=OH O cinnamic acid O coumarin CO2H O CO2H phenylacetic acid benzoic acid O flavonoid O O lignan 8. R=H tyrosine.0 Shikimates & phenylpropanoids (Dayrit) 6 . CO2H CO2H R NH2 phenylalanine.Shikimates comprise a large group of aromatic natural products.

Shikimic acid picks up three carbons from of phosphoenol pyruvate to form chorismic acid and prephenic acid. p-aminobenzoic acid phenylpropanoids 8.0 Shikimates & phenylpropanoids (Dayrit) 7 . ATP OH OH 2. PEP shikimate PO O _ CO 2 _ CO2 O OH 3 2 3 2 _ _ CO2 O 1 OH HO [3. Chorismic acid is converted to prephenic acid via a concerted [3.3]-sigmatropic shift.3]sigmatropic shift _ CO2 _ O2C 1 2 _ CO2 3 O CO2 3 3 2 3 1 _ CO2 OH chorismate 5-EPSP 1 _ O2C PO H 1 O 2 1 OH 2 _ CO2 OH p-hydroxybenzoic acid prephenate o-aminobenzoic acid. _ CO2 _ CO2 _ CO2 H H HO 1.

_ a O _ O CO2 O Prephenate is the precursor of phenylalanine and tyrosine.0 Shikimates & phenylpropanoids (Dayrit) 8 . -H2O Pyridoxamine transaminase OH phenylalanine prephenate b [O] _ _ O2C CO2 O NH2 _ CO2 CO2H O -CO2 O Pyridoxamine transaminase OH OH tyrosine 8. NH2 _ CO2 CO2H O a -CO2.

including tannins • C6-C2: phenyl ethyl compounds 8.0 Shikimates & phenylpropanoids (Dayrit) 9 . C6-C1 and C6-C2 The shikimate metabolites can be grouped according to the number of carbons atoms in the side chain. • C6: phenols and quinones • C6-C1: benzoic acid derivatives.C6.

MeO R OH 10 . C-methylation assists in biological electron transfer. the 1. O-methylation n from terpenes R MeO OH OH O O Me Me MeO MeO O Ubiquinone n R O 5-Demethoxy ubiquinone [O] Quinones are formed mainly from the polyketide and shikimate pathways. The biosynthesis of R OH ubiquinone.Routes to benzoquinones: A. [O] compound which 2. -CO 2 2. although other groups may produce quinones from extensive modification. [O] 3. is OH Me shown. Shikimatic acid Benzoquinones Homogentisic acid C6 Metabolites Benzoquinones Chroismic acid p-Hydroxybenzoic acid Phenylalanine Benzoquinones From p-Hydroxybenzoic acid: CO 2H CO 2H R= 1. Polyketides Hydroxybenzoic acids B.

0 Shikimates & phenylpropanoids (Dayrit) 11 .C6-C1. contain glucose and gallic acid joined by ester linkages. HO O HO OH O HO HO O O OH OO HO O OH corilagin O OH HO HO O OH OH OH O O OH OH O HO O HO OH O O HO OH O OH O O HO O O OH O HO HO OH O OH Turkish tannin HO OH 8. Tannins are a group of benzoic acid plant metabolites which precipitate proteins. which are hydrolyzable tannins. The gallotanins.

OH OH HO O OH HO HO HO OH OH O O O HO HO O O Gallic acid OH O HO OH HO OH Ellagic acid 8. These compounds are natural antioxidant in aqueous and micellar environments. Ellagic acid is also a naturally-occuring phytochemical pesticide and antimicrobial.0 Shikimates & phenylpropanoids (Dayrit) 12 . Gallic acid and ellagic acid are constituents of hydrolyzable tannins but these are found in many other natural products.Two benzoic acid derivatives of some interest are gallic acid and ellagic acid.

.” Planta Med.0 Shikimates & phenylpropanoids (Dayrit) OH OH 13 . Ellagitannis from banaba. R2=H Flosin B: R1=H..) OH HO OH OH OH R1 HO O HO HO HO O R2 H O O H H O H O O OH O OH OH OH CH2 O HO O O HO HO O O O O Lagerstroemin: R1=OH. “Ellagitannins from Lagerstroemia speciosa as Activators of Glucose Transport in Fat Cells. 2002. (Hayashi. R2=OH 8.Ellagitannins are hydrolyzable tannins which are formed from the condensation of a sugar core and ellagic acid units. Lagerstroemia speciosa. 173-5. were shown to increase uptake of adipocytes in rats. 68. et al. and could be responsible for lowering the blood glucose level.

CO 2H CO 2H CO 2H NH2 cinnamic acid phenylalanine [O] [O] CO 2H NH2 HO be nzoic acid [O] CO 2H TAL HO p-hydroxybenzoic acid [O] [O] HO CO 2H HO [O] CO 2H -o xidation NH2 HO HO HO CO 2H de carbo xylase.4-dihydroxyphenylalanine (DOPA) HO chorismic acid HO 4-hydroxycinnamic acid (p-coumaric acid) tyrosine CO 2H -o xidation [CH3] CO 2H CH3O CO 2H -o xidation NH2 HO HO HO ferulic acid do pamine vanillic acid 1. [Me] 1. [Me] OH CH3O HO CH3O CO 2H CO 2H -o xidation NH(CH3) HO adrenaline HO HO OCH3 sinapic acid OCH3 syring ic ac id 14 . -CO2 CO 2H pro tocatec huic acid OH gallic acid [CH3] CH3O HO HO HO caffe ic acid 3. [Me] 1. These compounds occur widely in plants. [O] 2.-o xidation PAL The benzoic and cinnamic acids are biosynthesized in a metabolic grid. [O] 2. [O] 2.

• The dotted arrow is a metabolic link to aromatic glucosinolates.. Curr Opinion in Plant Biol 2005. (Jorgensen et al. almonds. and the fruits and wilting leaves of the rose family (including cherries. 8:280–291) 8.Cyanogenic glycosides: C6-C2 • A cyanogenic glycoside has an aglycone with a cyanide group and an attached sugar. • Cyanogenic glycosides are found in cassava. and raspberries). apples. apricots. plums. Sorghum (Sorghum bicolor) expresses cyanogenic glycosides in its roots and thus is resistant to pests such as rootworms.0 Shikimates & phenylpropanoids (Dayrit) 15 . Cyanogenic glycosides release the poisonous hydrogen cyanide enzymatically. peaches.

cress. • About 120 glucosinolates are known in plants. These substances are also responsible for the bitter or sharp taste of many common foods such as mustard. derived from methionine. alanine.0 Shikimates & phenylpropanoids (Dayrit) 16 . cabbage. broccoli. cauliflower. horseradish. or indolic derived from tryptophan. leucine. radish. aromatic. derived from phenylalanine and tyrosine. 8. nitrogen and a group derived from glucose. • Glucosinolates act as natural pesticides and defense against herbivores. and turnip. where the R group is alkyl. Brussels sprouts. or valin.Glucosinolates • The glucosinolates are found in OH - O HO HO OSO3 S N HO HO (R group variable) Brassicales and contain sulfur.

Phenyl propanoids: C6-C3
• The phenylpropanoid metabolism is unique to plants.
• Many intermediates and end products of the phenylpropanoid
pathway play important roles in plants as phytoalexins,
antioxidants, antiherbivory compounds, UV protectants,
pigments, and aroma compounds. Phenylpropanoids polymerize
to form lignins, which are essential components of the cell wall
stability.
• Phenylpropanoid biosynthesis is one of the best-studied
pathways in plants. The enzymes of the phenylpropanoid pathway
are organized in multi-enzyme complexes and there is evidence
for the coordinated expression of genes and enzymes. Genes
encoding enzymes of this pathway are developmentally and
tissue-specifically regulated and may be induced by
environmental stresses such as nutrient deficiency, exposure to
cold, UV light, and8.0pathogen
attack.
Shikimates & phenylpropanoids
(Dayrit)
17

Phenylalanine and tyrosine are deaminated by phenylalanine ammonia lyase
(PAL) or tyrosine ammonia lyase (TAL) to cinnamic acids. The cinnamic acids
(C6-C3) are the precursors to the phenyl propanoids, coumarins, styrenes,
benzoic acids, phenols, and flavonoids. A multi-enzyme complex enables
coordinated action of PAL and cinnamate-4-hydroxylase (C4H) which control
the flux of intermediates in phenylpropanoid biosynthesis.
NH2

CO2H
CO2H

PAL
or
TAL

Ar - C3: cinnamaldehydes
cinnamyl alcohols
aryl propanes

Ar - C3: coumarins

C4H
R

CO2H

R1

R3

R

phenylalanine, R=H
tyrosine, R=OH

R2
+ 3 x Ac

cinnamic acids
Ar - C2: styrenes
acetophenones

flavonoids

Ar: phenols
quinones

Ar - C1: benzoic acids
benzyl aldehydes
benzyl alcohols

8.0 Shikimates & phenylpropanoids (Dayrit)

18

HO CO2H

Examples of
cinnamic acids
and the C6-C3
derivatives.
Cinnamic acids
themselves do
not usually
occur in the
free form but
are isolated as
glycosides.
Cinnamic acids
are precursors
of lignans and
lignins.

O
HO

OH

O
OH

3-caffeoylquinic acid (chlorogenic acid).
First isolated in 1846 from coffee, it has since
been found to be a common plant compound.
It functions as an allelopathic substance in
sunflower.

OH
OH

HO
O O

OH

HO
HO
OC

OH

CH3O

OH

RO
coniferyl alcohol, R=H
coniferin, R=glucosyl

O
2-caffeoylarbutin

CH3O
eugenol
Eugenol and saffrole are well-known
constituents of flavor and spice plants.
They are precursors to lignins and lignans.

HO

O
saffrole
O

8.0 Shikimates & phenylpropanoids (Dayrit)

19

particularly the Umbelliferae and Rutacea families.0 CH3 OCH3 R2 6 7 5 4 Z 3 2 1 8 Shikimates O (Dayrit) R1O & phenylpropanoids O RO CO2H O-glu 20 . CO2H HO CO2H O NH 2 HO HO tyrosine OH O caffeic acid CH2 CH CO2H HO OH HO HO CO2H CO2H rosmarinic acid Rosmarinic acid is a naturally-occurring anti-histamine compound from tsaang gubat (Ehretia macrophylla). They are widely distributed in plants. OH NH 2 HO phenylalanine Coumarins are aromatic lactone C6-C3 derivatives.Examples of cinnamic acids and the C6-C3 derivatives. CO2H [O] RO CO2H CO2H glucose RO O-glu RO OH E umbelliferone herniarin skimmin aesculetin scopoletin R1 R2 H H CH3 H glu H H OH 8. Rosmarinic acid is a dimer of two different C6-C3 units.

0 Shikimates & phenylpropanoids (Dayrit) 21 . O O HH O 8.Examples of coumarin compounds. O O-H O CO2H H OH C HO O O H O O O O-H O Some microorganisms (such as Aspergillus fumigatus) transform coumarin from plants (such as grass) to produce dicoumarol. O H H O O CH2 O O O O dicoumarol HO OH O O O Furobinordenatin is a coumarin from Citrus plants. Dicoumarol is a powerful blood anticoagulant and can cause fatal hemmorages in cattle that eat the hay.

. Biol. Plant Physiol. Lewis.Lignans are phenylpropanoid dimers. 453 (2000). in Science.. 6. 362 (1997). They can be rationalized by formation by coupling of resonance-stabilized by radicals with the assistance of “dirigent” proteins. O CH3O HO CH 3O OH H O O OH . 143 (1999)) 22 . 123. OCH3 OCH3 OH H Proposed coupling intermediate (+/-)-Dehydrodiconiferyl alcohols + OCH3 OCH3 OH OH O O H H O O HO HO OCH3 (+/-)-Pinoresinols OCH3 (+)-Pinoresinol + Other dimers 8.G. Chem. 275.0 Shikimates &etphenylpropanoids (Dayrit) (N. al. OH oxidase with guiding (dirigent) protein oxidase only OCH3 OH H OH .

[O] CH 3O CH3O O.0 Shikimates & phenylpropanoids (Dayrit) OCH3 OH (+)isolariciresinol 23 .The diversity of lignan structures can be rationalized by bond formation via different radical sites. CH 2OH CH2OH CH 2OH . OH CH3O CH2OH O CH2OH CH3O O OCH3 O H+ O HO OCH3 HO O [H] OCH 3 CH 3O CH 2OH HO CH 2OH OH O OCH 3 O H+ OCH3 OCH 3 HO (+)pinoresinol O H+ CH 3O CH2OH HO CH2OH 8.

CH3O . CH3O O O O OCH3 CH3O O OCH3 H+ O OCH3 HO licarin A (from eugenol) 8. H .0 Shikimates & phenylpropanoids (Dayrit) 24 .The diversity of lignan structures can be rationalized by bond formation via different radical sites.

cl)  Lignin has far-reaching impacts on agriculture.  Lignin is the second most abundant polymer on earth.scielo.4 × 1012 kg of carbon sequestered into terrestrial plant material each year. making phenylpropanoid metabolism a globally important part of plant biochemistry. (/www. next to cellulose. accounting for about 30% of the more than 1. industry and the environment. a complex three-dimensional polymer that is a principal structural component of plant cell walls. 8.0 Shikimates & phenylpropanoids (Dayrit) 25 .Lignins  The majority of carbon in the phenylpropanoid group is channeled toward the synthesis of lignin. Lignin is a major carbon sink in the biosphere.

Similar to the lignans. they are formed by coupling between different radicals arising from phenylpropanoids. O OCH3 alkyl. CH3O O 8. + alkyl. + Ph. + alkyl. HO OCH3 OH HO Lignins are extensively crosslinked phenylpropanoid polymers.O OH CH3O O HO OCH3 O Ph. O.0 Shikimates & phenylpropanoids (Dayrit) 26 . + alkyl. Lignins contribute to the strength and robustness of plants and as a protective barrier against biochemical degradation by microorganisms. HO O O OCH3 OH Ph.

0 Shikimates & phenylpropanoids (Dayrit) 27 Humphreys and Chapelle. 8. 4CL. p-coumarate 3-hydroxylase C4H. ferulate 5-hydroxylase PAL. caffeoyl CoA O-methyltransferase CCR. phenylalanine ammonia-lyase pCCoA3H. caffeic acid/5-hydroxyferulic acid O-methyltransferase CQT. cinnamyl alcohol dehydrogenase CCoAOMT. . 5:224–229. p-coumaryl CoA 3-hydroxylase SAD.Intermediates and enzymes of the lignin pathway. hydroxycinnamoyl CoA:shikimate hydroxycinnamoyltransferase F5H. cinnamoyl CoA reductase COMT. 4-(hydroxy)cinnamoyl CoA ligase C3H. sinapyl alcohol dehydrogenase. cinnamate 4-hydroxylase CAD. hydroxycinnamoyl CoA:quinate hydroxycinnamoyltransferase CST. Current Opinion in Plant Biology 2002.

 Flavonoids are physiologically important because of their many antioxidant properties. Flavonoids have a characteristic “C6-C3C6” structure.  Most flavonoids. Flavonoids are universally distributed among vascular plants and are found throughout the plant.Flavonoids  The flavonoids are a very widely occurring group of natural products.0 Shikimates & phenylpropanoids (Dayrit) 28 .000 flavonoids identified in plants. There are over 5. except for the catechins.roots. are naturally found in their glycosylated form. seeds. and a -pyrone C ring. 8. with three rings: an aromatic A and B ring. leaves and flowers—where they play important functions. bark. fruit.

and allelopathic. 8.0 Shikimates & phenylpropanoids (Dayrit) 29 . reds.OH Flavonoids O HO OH O OH luteolin Flavonoids have attracted wide interest due to the following: a. the chlorophylls mask these colors. for example. and yellows) yellows are produced by the flavonoid group known as the anthocyanidins. Distribution of flavonoids. are known to be antifungal. purples. often in various methylated and glycosylated forms. Functions of flavonoids in plants. The highly oxygenated flavonoids are UV-active and are thought to protect the plant against UV radiation. A number of flavonoids. In leaves. antibacterial. The colored pigments in flowers of angiosperms (blues. Various flavonoids are believed to play specific roles in the physiology of plants. They are present in most parts of the plant. b. The flavonoids are one of the most numerous and widespread groups of secondary metabolites.

Further oxidation and methylation occur after flavonoid ring formation. • the Extensive biosynthetic studies have been carried out using tissue culture of parsley. 8. Biological activity of flavonoids. Flavonoids are formed from the condensation of a phenylpropanoid + triketide. The flavonoids can be subdivided according into oxidation level and position at three rings. In addition. and have found use in protection against weak arteries.OH Flavonoids O HO OH O OH luteolin c. This is thought to explain its anti-inflammatory and cancerprotective properties. flavonoids have been shown to strengthen blood capillaries. A number of flavonoids have been shown to protect cells against oxidative attack.0 Shikimates & phenylpropanoids (Dayrit) 30 . Chalcone is the entry point to the flavonoids. strokes and • hemorrhoids.

R=OH - 1. NADPH 2. PAL / TAL 2. -CoASH dihydropyrone R O Overview of the condensation of phenylpropanoid + (3 x acetyl CoA). -CO2. O O -CoASH * * O * styryl pyrone CO2- 1. R=H tyrosine. R O * CoA -S 2. -CoASH R R OH HO to the flavonoids * * -CoASH O * O * O chalcone S-CoA * O * OH chalcone synthase O 31 . -CoASH O benzal acetone CoA-S * R O O O -CoASH O CO2- * 1. OH O * R CoA-S * O CoA -S 2. -CoASH R 1. -CO2. -CO2. CoA -S * O 2. -CO2. CoA ligase CoA-S -O C 2 NH2 O CO2- phenylalanine.R R 1.

-CoASH R 1. - * OH (C6-C3) + C2. R=OH - 1. The addition of acetyl CoA probably occurs stepwise yielding intermediates with the following structures: styryl pyrone CO2- 32 . -CO2. -CO2. R=H tyrosine. CoA ligase CoA-S -O C 2 NH2 O CO2- phenylalanine. -CO2. -CoASH dihydropyrone R O (C6-C3) + C4. * O * (C6-C3) + C6. -CoASH O benzal acetone CoA-S R O * O CO2- 1. (C6C3). R CoA -S O * 2. R * O CoA -S 2. with three acetyl CoA units (3 x C2). NADPH 2.R R 1. CoA-S -CoASH * * O O O The first member of the flavonoid group is chalcone. PAL / TAL 2. O -CoASH O Flavonoids arise from condensation of a phenylpropanoid.

-CoASH R R OH HO to the flavonoids * * -CoASH O * O * O chalcone S-CoA * O * OH chalcone synthase (polyketide cyclization) O 33 . OH R CoA-S * O O * 2. The first member formed is chalcone. -CO2. * * O * styryl pyrone CO2- 1. -CO2. CoA -S * O 2. -CoASH O benzal acetone CoA-S * R O O O -CoASH O CO2- * 1.2. -CoASH dihydropyrone R O CoA -S O O -CoASH Flavonoids arise from condensation of phenylpropanoid + triketide. -CO2.

O O chalcone O flavanone isoflavanone + O O OH OH flavan-3.0 Shikimates & phenylpropanoids (Dayrit) 34 .5' Oxidation Level 8 7 1 4' 6' 1 9 O 2 3' 1' 2' 6 5 10 3 4 flavone O 2 OH O dihydrochalcone flavan-3-ol (catechin) O O 3 The principal structural feature of the flavonoids is C6-C3-C6. The flavonoids can be subdivided by oxidation level and oxidation position.4-diol (leucoanthocyanidinin) flavylium 8.

Oxidation level O O 4 O O isoflavone O flavone aurone + O O OH O OH anthocyanidin flavanonol (dihydroflavonol) The principal structural feature of the flavonoids is C6-C3-C6. O 5 OH O flavonol 8.0 Shikimates & phenylpropanoids (Dayrit) 35 . Flavonoids can be subdivided by oxidation level at the C ring.

0 Shikimates & phenylpropanoids (Dayrit) 36 .Six flavonoid subgroups 1. Flavonols: 3. Flavones: Apigenin Luteolin Kaempferol Quercetin 2. Flavanones: Naringenin 8.

Six flavonoid subgroups 4. Isoflavones: 5.0 Shikimates & phenylpropanoids (Dayrit) 37 . Anthocyanidins: Cyanidin 8. Flavan-3-ols: Epicatechin Epigallocatechin 6.

Flavonoids can be further grouped according to the specific position of oxidation at the three rings.0 Shikimates & phenylpropanoids (Dayrit) chrysoeriol OH 4' + 4' 4' O HO OH OH OH O Biosynthetic studies in tissue culture of parsley: Chalcone is the entry to the flavonoids. Note that further oxidation and methylation occur after flavonoid ring formation.OH OH 7 OH O B O HO OH HO A C 5 4 naringenin (flavanone) O OH chalcone 4' flavones flavonols 7 7 5 5 4 OH O apigenin (flavone) [O] O HO OH 2 7 5 OH OH luteolin 4' 3' O HO OCH3 2 7 5 OH O OH 4 OH O quercetinin 2 7 OH 4' 3' O HO 5 4 OH [Me] OH anthocyanin 4' 3' 2 5 [Me] OH kaempferol (flavonol) 7 4 O O O HO OH OH [O] OH 4' 3' 5 4 OH O HO O HO 7 OCH3 4 OH 8. isohamnetin 38 .

Biochemistry of Secondary Metabolites 2010). . There are some taxonomic patterns but many questions remain.Occurrence of flavonoids in various plants (Wink.

- O CO2 O O O HO OH HO bismalonyl isorhamnetin-3. glycosylation and acetylation are commonly observed modifications. For example.0 Shikimates & phenylpropanoids (Dayrit) 40 .7-bisglucoside 8.OH HO OH Glc-O O O OH OH OH UDP-glucose O UDP OH O UDP-glucose UDP OH OH Glc -O HO O OH OH O-Glc O O 2x CoASH O O O O - CO2 OH 2x malonyl CoA OH O Numerous flavonoids are formed by further modifications of the basic flavonoid rings.

0 Shikimates & phenylpropanoids (Dayrit) OCH3 formononetin 41 . Labeling studies on isoflavonoids OH HO * # ^ HO2C HO NH2 O * # ^ O * # ^ O O 8.Isoflavonoids Isoflavonoids are formed from flavonoids by 1.2-migration of the B-ring from the 2. A. Studies using labeled phenylalanine are consistent with the proposed origin of the isoflavonoids.to the 3-position.

The nodD gene-encoded proteins of Rhizobia have been shown to physically bind to flavonoids and isoflavonoids. are essential for plant-microbe interactions.0 Shikimates & phenylpropanoids (Dayrit) 42 . which play key roles in non-specific plant defense against bacterial and fungal pathogens.HO Isoflavonoids O O OCH3 • The isoflavonoids. • Different isoflavonoids are also either precursors to. The activation of isoflavonoid synthesis during the disease resistance response is important for providing these many defense compounds. and this ligand association initiates transcription of the nod operon leading to root nodule formation. such as chemoattractants and signal molecules for symbiotic Rhizobium bacteria. or are themselves the major phytoalexins in legumes. 8. which are produced in legumes.

• Isoflavones are produced at significant levels only in tissues where the phenylpropanoid pathway activity is elevated. 8. An enzyme found almost exclusively in the legumes. isoflavone synthase (IFS). converts the phenylpropanoid pathway intermediates tetrahydroxy-chalcone (naringenin) and trihydroxy-chalcone (isoliquiritigenin) into the isoflavones genistein and daidzein.HO Isoflavonoids O O OCH3 • Isoflavonoid synthesis is a branch of the general phenylpropanoid pathway that exists in all higher plants. such as in floral tissues. and in tissues where expression of a heterologous transcription factor was used to activate genes of the phenylpropanoid pathway. in UV-treated tissues.0 Shikimates & phenylpropanoids (Dayrit) 43 . respectively.

isoflavanone O O O O isoflavone O O O O O O 3-arylcoumarin O O O O O rotenoid dehydrorotenoid O O 8.0 Shikimates & phenylpropanoids (Dayrit) 44 . dehydropterocarpan The isoflavonoids are found mostly in the coumestan Leguminosae family.O O Flavonoids are converted pterocarpan enzymatically to the isomeric isoflavonoids.

0 Shikimates & phenylpropanoids (Dayrit)O O 45 . Biosynthesis of rotenone OPP [O] HO 1. another closely related compound: milletone O O H s s O O O O H O H rotenone OCH3 OCH3 O H 8. but is considered safe for mammals. Rotenone is found in mangrove plants and is a fish poison. [O] 2. ATP H3C O O isoflavone HO H2C O O O O OCH3 OCH3 [H-] OCH3 OCH3 NADPH HO O O H HO O O H O OPP H O OCH3 H OCH3 OCH3 OCH3 Rotenone is one of the best known of the isoflavonoids.B.

A.Anthocyanins are the sugar. List of the best-known anthocyanins and anthocyanidins. Anthocyanins are water-soluble pigments in flowers. They also impart many of the colors of fruit juices and wines. leaves and fruits. Substituents and Color R: R5' OH + O HO R3' 3 5 3' 5' Name Color H H H H pelargonidin red H H OH H cyanidin blue H H OH OH delphinidin deep purple Glc Glc OH H cyanin colorless O-R3 O-R5 8.derivatives of the anthocyanidins (the aglycone).0 Shikimates & phenylpropanoids (Dayrit) 46 . A.

B.B. Anthocyanin color is produced in compounds which can achieve a planar conformation which gives maximum delocalization. this conformation is possible if R3 is small 8.0 Shikimates & phenylpropanoids (Dayrit) 47 . Structure and Color R5' R5' + O HO OH R3' HO O H + OH R3' H O R3 - O-R3 O-R5 O-R5 non-planar conformation is colorless. this form predominates if R3 is large extended resonance form is colored.

Anthocyanins and flower color (“The Big Bloom: Birth of Flowering Plants. National Geographic. • The UV pattern of many flowers is due to anthocyanins.0 Shikimates & phenylpropanoids (Dayrit) 48 . in the UV range which is invisible to most animals but visible to bees. July 2002) • The yellow day lily has a near uniform hue in the visible spectral range. the lily has a two-toned pattern. 8. However.

As the autumn? temperature drops and the days shorten. which are always present. gives leaves its predominant color. anthocyanins are actively formed in the leaves during autumn. purple and magenta hues.0 Shikimates & phenylpropanoids (Dayrit) 49 . orange and gold hues. • Anthocyanins give rise to the reds. • Carotenoids are responsible for the yellow. Different species of trees contain various types of carotenoids. revealing the presence of the other leaf pigments. It is red. 8. it is destroyed enzymatically. which is green. orange. In contrast to the carotenoids.Leaf color is due to several Anthocyanins and autumn leaves compounds: Why do leaves turn yellow. purple and magenta during responsible for photosynthesis. • Chlorophyll.

What is the special role of anthocyanins? red. 8.Anthocyanins and autumn leaves Why do leaves turn yellow. purple and magenta during autumn? It is hypothesized that anthocyanins protect the leaf from free radicals which are produced by the destruction of the photosynthetic system. The net effect is that anthocyanins slow down leaf death and abscission. orange. They provide some environmental protection from UV radiation and nutrient deficiency.0 Shikimates & phenylpropanoids (Dayrit) 50 .

HO O OH OH HO O OH OH OH OH OH (-)-epicatechin (-)-catechin OH HO O OH OH HO O OH OH OH OH OH (+)-epicatechin (+)-catechin 8.A. 51 .0 Shikimates & phenylpropanoids (Dayrit) flavan-3-ols which are believed to be biosynthetically related to the anthocyanidins and may be produced during the extraction of anthocyanidins. OH + O HO Catechins are OH HO O OH OH OH catechin anthocyanidin OH B. The best known catechins are ()catechin and ()epicatechin which are major constituents of tea.

Condensed tannins are polymeric compounds made up of catechin monomers. OH R HO O OH OH OH OH OH HO O OH n x HO O OH OH OH OH OH OH (-)-epicatechin HO O OH OH OH 8.0 Shikimates & phenylpropanoids (Dayrit) R 52 .

0 Shikimates & phenylpropanoids (Dayrit) 53 .8.

(A) Classical pathway. MK is converted by MenA and MenG. which catalyze prenylation and methylation.4-dihydroxy-2-naphthoate by MenB. followed by the attachment of coenzyme A to yield o-succinylbenzoylCoA by MenE. . o-Succinylbenzoyl-CoA is then converted into 1.MK biosynthetic pathways. This compound is dehydrated by MenC to osuccinylbenzoate. In the last two steps of the pathway. respectively. respectively. Red and black bold lines show carbons originated from erythrose-4-phosphate and phosphoenolpyruvate. Chorismate is converted into isochorismate by MenF (isochorismate synthase) and then into 2-succinyl-6-hydroxy-2.4cyclohexadiene-1-carboxylate by MenD.

coelicolor A3(2). . Based on the annotation of the open reading frames of S. (B) Alternative pathway. Green and blue bold lines indicate two carbon units derived from C-5 and C-6 of glucose via different metabolic pathways. SCO4490 (decarboxylation).MK biosynthetic pathways. we presumed that SCO4491 (prenylation). and SCO4492 (decarboxylation) would be involved in the late step of the MK biosynthetic pathway. SCO4556 (methylation).

4-(hydroxy)cinnamoyl CoA ligase C3H. caffeoyl CoA O-methyltransferase CCR. COMT. cinnamyl alcohol dehydrogenase CCoAOMT. sinapyl alcohol dehydrogenase. 56 . phenylalanine ammonia-lyase Shikimates pCCoA3H& . cinnamate 4-hydroxylase CAD. Jorgensen et al. cinnamoyl CoA reductase 8. caffeic acid/5-hydroxyferulic acid O-methyltransferase CQT. hydroxycinnamoyl CoA:shikimate hydroxycinnamoyltransferase F5H.Metabolons of Phenylpropanoid Genes • A metabolon is a temporary functional complex of several sequential enzymes held together by noncovalent interactions in a given metabolic pathway. p-coumarate 3-hydroxylase C4H. p-coumaryl phenylpropanoids CoA 3-hydroxylase (Dayrit) SAD. • Enzymes that are known to be present as multiple isoforms are marked with an asterix. • Organization of the branched pathways of phenylpropanoid metabolism within separate individual metabolons.0 • Enzymes that participate in multiple branches are shown in red and blue.. Curr Opinion in Plant Biol 2005. ferulate 5-hydroxylase PAL. hydroxycinnamoyl CoA:quinate hydroxycinnamoyltransferase CST. whereas enzymes that are thought to be unique to specific pathways are shown in other colors. 8:280–291 4CL.

New experimental approaches document the importance of channeling in the synthesis of isoprenoids.Metabolons and the Biosynthesis of Natural Products • Metabolon formation and metabolic channeling in plant secondary metabolism enable plants to effectively synthesize specific natural products and to avoid metabolic interference. phenylpropanoids. (Jorgensen et al. • Metabolon formation and metabolic channeling in natural-product synthesis facilitate attempts to genetically engineer new pathways into plants to improve their content of valuable natural products.0 Shikimates & phenylpropanoids (Dayrit) 57 . flavonoids and cyanogenic glucosides.. They also offer the opportunity to introduce new traits by genetic engineering to produce plant cultivars that adhere to the principle of substantial equivalence. 8:280–291) 8. alkaloids. • Channeling can involve different cell types. take advantage of compartmentalization within the same cell or proceed directly within a metabolon. Curr Opinion in Plant Biol 2005.

7.4’-trihydroxyisoflavone 4’-Omethyltransferase D7OMT: daidzein 7-O-methyltransferase HID: 2-hydroxyisoflavanone dehydratase 8.. 8:280–291) IFS: 2-hydroxyisoflavanone synthase HI4’OMT: 2. and conversion to phytoalexins. Curr Opinion in Plant Biol 2005. (Jorgensen et al.Metabolic channeling of biosynthesis: flavonoids  isoflavonoids  phytoalexins Biosynthesis of O-methylated isoflavonoids in licorice.0 Shikimates & phenylpropanoids (Dayrit) 58 .

lignins. catechins 8. isoflavonoids. acetophenones  C6-C3: phenyl propanoids: cinnamaldehydes. scent (some aryl propanes). benzyl alcohols  C6-C2: phenylethyl amines. styrenes. lignans  C6-C3-C6: flavonoids. benzaldehydes. ranging from structural (lignins). and plant defense (flavonoids and isoflavonoids). aryl propanes. The shikimates can be grouped by C6-Cn classification:  C6: phenols and quinones  C6-C1: benzoic acids.Summary Many of the aromatic compounds found in higher plants belong to the shikimates. flower and leaf coloration (anthocyanins and flavonoids).0 Shikimates & phenylpropanoids (Dayrit) 59 . The shikimates have for a diverse range of properties and functions in plants.

C6-C2: styrenes.glucose shikimic acid Summary of the shikimates C6-C1: p-hydroxybenzoic acid chorismic acid C6-C1: o-hydroxybenzoic acid (salicylic acid) C6-C1: p-aminobenzoic acid prephenic acid phenylalanine. tyrosine C6-C2: phenylethylamines C6-C3: cinnamic acids C6-C3: cinnamaldehydes C6-C3: cinnamic alcohols C6-C3: coumarins C6-C3: arylpropanes C6-C1: o-aminobenzoic acid (anthranilic acid) indole. quinones C6-C1: benzoic acids. tryptophan +3 x (C2) C6: phenols. benzaldehydes. benzyl alcohols acetophenones C6-C3-C6: flavonoids isoflavonoids catechins condensed tannins .