Abstract
Plant natural products have been used since ancient times as medicines and herbal remedies. Over the past two decades, the results of population and intervention studies, or assays in animal or cell model systems, have revealed positive health beneficial effects for various classes of phytochemicals, particularly polyphenols. The results of such studies have ignited an interest in being able to manipulate the levels of such bioactive compounds in plants using biotechnological approaches. Although still in its infancy, this technology promises to deliver health benefits to humans and animals through direct consumption of genetically-modified or -enhanced dietary plant materials. We here review the strategies currently being used for engineering two classes of nutraceuticals, the proanthocyanidins and the isoflavones, in transgenic plants. We also provide an overview of recent advances in our understanding of the biosynthesis of these classes of compounds.
Similar content being viewed by others
Abbreviations
- AHA:
-
Autoinhibited H+-ATPase isoform
- ANR:
-
Anthocyanidin reductase
- ANS:
-
Anthocyanidin synthase
- DFR:
-
Dihydroflavonol reductase
- DMAPP:
-
Dimethylallyl pyrophosphate
- ER:
-
Estrogen receptor
- F3H:
-
Flavanone 3-hydroxylase
- F3′H:
-
Flavonoid 3′-hydroxylase
- FLS:
-
Flavonol synthase
- FNS:
-
Flavone synthase
- GPP:
-
Geranyl pyrophosphate
- GSPE:
-
Grape seed proanthocyanidin extract
- GST:
-
Glutathione S-transferase
- 2HID:
-
2-Hydroxyisoflavanone dehydratase
- 2HIS:
-
2-Hydroxyisoflavanone synthase
- IFS:
-
Isoflavone synthase
- LAR:
-
Leucoanthocyanidin reductase
- LDL:
-
Low density lipoprotein
- MATE:
-
Multidrug and toxic efflux transporter
- 2-OG:
-
2-Oxoglutarate
- OMT:
-
O-methyltransferase
- PA:
-
Proanthocyanidin
- PAL:
-
Phenylalanine ammonia-lyase
- PAP:
-
Production of anthocyanin pigmentation
- TT:
-
Transparent testa
- TTG:
-
Transparent Testa Glabra
- UGT:
-
UDP glycosyltransferase
References
Achnine L, Huhman DV, Farag MA et al (2005) Genomics-based selection and functional characterization of triterpene glycosyltransferases from the model legume Medicago truncatula. Plant J 41:875–887
Adlercreutz H (2002) Phyto-oestrogens and cancer. Lancet Oncol 3:364–373
Ahmad N, Gupta S, Mukhtar H (2000) Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor kB in cancer cells versus normal cells. Arch Biochem Biophys 376:338–346
Akashi T, Aoki T, Ayabe S (1998) Identification of a cytochrome P450 cDNA encoding (2S)-flavanone 2-hydroxylase of licorice (Glycyrrhiza echinata L.; Fabaceae) which represents licodione synthase and flavone synthase II. FEBS Lett 431:287–290
Akashi T, Aoki T, Ayabe S (1999a) Cloning and functional expression of a cytochrome P450 cDNA encoding 2-hydroxyisoflavanone synthase involved in biosynthesis of the isoflavonoid skeleton in licorice. Plant Physiol 121:821–828
Akashi T, Aoki T, Ayabe S (2005) Molecular and biochemical characterization of 2-hydroxyisoflavanone dehydratase. Involvement of carboxylesterase-like proteins in leguminous isoflavone biosynthesis. Plant Physiol 137:882–891
Akashi T, Fukuchi-Mizutani M, Aoki T et al (1999b) Molecular cloning and biochemical characterization of a novel cytochrome P450, flavone synthase II, that catalyzes direct conversion of flavanones to flavones. Plant Cell Physiol 40:1182–1186
Akashi T, Sawada Y, Shimada N et al (2003) cDNA cloning and biochemical characterization of S-adenosyl-l-methionine: 2,7,4′-trihydroxyisoflavnone 4′-O-methyltransferase, a critical enzyme of the legume isoflavonoid phytoalexin pathway. Plant Cell Physiol 44:103–112
Akashi T, VanEtten HD, Sawada Y et al (2006) Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis. Phytochemistry 67:2525–2530
Akiyama T, Ishida J, Nakagawa S et al (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262:5592–5595
Anzellotti D, Ibrahim RK (2000) Novel flavonol 2-oxoglutarate dependent dioxygenase: affinity purification, characterization, and kinetic properties. Arch Biochem Biophys 382:161–172
Bagchi D, Bagchi M, Stohs SJ et al (2000) Free radicals and grape seed proanthocyanidn extract: importance in human health and disease prevention. Toxicol 148:187–197
Baird D, Umbach D (1995) Dietary intervention study to assess estrogenicity of dietary soy, among postmenopausal women. Clin Endocrinol 80:1685–1690
Barron D, Ibrahim R (1996) Isoprenylated flavonoids—a survey. Phytochemistry 43:921–982
Barry TN, McNabb WC (1999) The implications of condensed tannins on the nutritive value of temperate forages fed to ruminants. Br J Nutr 81:263–272
Baudry A, Heim MA, Dubreucq B et al (2004) TT2, TT8, and TTG1 synergistically specify the expression of BANYULS and proanthocyanidin biosynthesis in Arabidopsis thaliana. Plant J 39:366–380
Baxter IR, Young JC, Armstrong G et al (2005) A plasma membrane H+−ATPase is required for the formation of proanthocyanidins in the seed coat endothelium of Arabidopsis thaliana. Proc Natl Acad Sci USA 102:2649–2654
Boersma BJ, Barnes S, Kirk M et al (2001) Soy isoflavonoids and cancer—metabolism at the target site. Mut Res 480–481:121–127
Bogs J, Downey MO, Harvey JS et al (2005) Proanthocyanidin synthesis and expression of genes encoding leucoanthocyanidin reductase and anthocyanidin reductase in developing grape berries and grapevine leaves. Plant Physiol 139:652–663
Bogs J, Ebadi A, McDavid D et al (2006) Identification of the flavonoid hydroxylases from grapevine and their regulation during fruit development. Plant Physiol 140:279–291
Bogs J, Jaffé FW, Takos AM et al (2007) The grapevine transcription factor VvMYBPA1 regulates proanthocyanidin synthesis during fruit development. Plant Physiol 143:1347–1361
Borevitz J, Xia Y, Blount JW et al (2000) Activation tagging identifies a conserved MYB regulator of phenylpropanoid biosynthesis. Plant Cell 12:2383–2393
Bowles D, Lim E, Poppenberger B et al (2006) Glycosyltransferases of lipophilic small molecules. Annu Rev Plant Biol 57:567–597
Byrne PF, McMullen MD, Snook ME et al (1996) Quantitative trait loci and metabolic pathways: Genetic control of the concentration of maysin, a corn earworm resistance factor, in maize silks. Proc Natl Acad Sci USA 93:8820–8825
Clemens S, Barz W (1996) Cytochrome P450-dependent methylenedioxy bridge formation in Cicer arietinum. Phytochemistry 41:457–460
Cornwell T, Cohick W, Raskin I (2004) Dietary phytoestrogens and health. Phytochemistry 65:995–1016
Deavours BE, Dixon RA (2005) Metabolic engineering of isoflavonoid biosynthesis in alfalfa (Medicago sativa L.). Plant Physiol 138:2245–2259
Deavours BE, Liu C-J, Naoumkina M et al (2006) Functional analysis of members of the isoflavone- and isoflavanone O-methyltransferase enzyme families from the model legume Medicago truncatula. Plant Mol Biol 62:715–733
Debeaujon I, Peeters AJM, Leon-Kloosterziel KM et al (2001) The TRANSPARENT TESTA 12 gene of Arabidopsis encodes a multidrug secondary transporter-like protein required for flavonoid sequestration in vacuoles of the seed coat endothelium. Plant Cell 13:853–871
Deluc L, Barrieu F, Marchive C et al (2006) Characterization of a grapevine R2R3-MYB transcription factor that regulates the phenylpropanoid pathway. Plant Physiol 140:499–511
Denis L, Morton M, Griffiths K (1999) Diet and its preventive role in prostatic disease. Eur Urol 35:377–387
Dewick PM (1993) Isoflavonoids. In: Harborne JB (ed) The flavonoids: advances in research since 1986. Chapman and Hall, London, pp 117–238
Dixon RA (2004) Phytoestrogens. Annu Rev Plant Biol 55:225–261
Dixon RA, Xie DY, Sharma SB (2005) Proanthocyanidins—a final frontier in flavonoid research? New Phytol 165:9–28
Dufresne CJ, Farnworth ER (2001) A review of latest research findings on the health promotion properties of tea. J Nutr Biochem 12:404–421
Epifano F, Genovese S, Menghini L et al (2007) Chemistry and pharmacology of oxyprenylated secondary plant metabolites. Phytochemistry 68:939–953
Foo LY, Lu Y, Howell AB et al (2000) The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry 54:173–181
Foo LY, Newman R, Waghorn G et al (1996) Proanthocyanidins from Lotus corniculatus. Phytochemistry 41:617–624
Formica JV, Regelson W (1995) Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol 33:1061–1080
Fukui Y, Tanaka Y, Kusumi T et al (2003) A rationale for the shift in colour towards blue in transgenic carnation flowers expressing the flavonoid 3′,5′-hydroxylase gene. Phytochemistry 63:15–23
Furukawa T, Maekawa M, Oki T et al (2007) The Rc and Rd genes are involved in proanthocyanidin synthesis in rice pericarp. Plant J 49:91–102
Gagnon H, Tahara S, Ibrahim RK (1995) Biosynthesis, accumulation and secretion of isoflavonoids during germination and development of white lupin (Lupinus albus L.). J Exp Bot 46:609–616
Gaitan E, Cooksey R, Legan J et al (1995) Antithyroid effects in vivo and in vitro of vitexin: a C-glucosylflavone in millet. J Clin Endocrinol Metabol 80:1144–1147
Haagen Y, Unsöld I, Westrich L, et al (2007) A soluble, magnesium-independent prenyltransferase catalyzes reverse and regular C-prenylations and O-prenylations of aromatic substrates. FEBS Lett 581:2889–2893
Harborne JB, Williams CA (2000) Advances in flavonoid research since 1992. Phytochemistry 55:481–504
He XZ, Dixon R (2000) Genetic manipulation of isoflavone 7-O-methyltransferase enhances the biosynthesis of 4′-O-methylated isoflavonoid phytoalexins and disease resistance in alfalfa. Plant Cell 12:1689–1702
He XZ, Reddy JT, Dixon RA (1998) Stress responses in alfalfa (Medicago sativa L.) XXII. cDNA cloning and characterization of an elicitor-inducible isoflavone 7-O-methyltransferase. Plant Mol Biol 36:43–54
He XZ, Wang XQ, Dixon RA (2006) Mutational analysis of the Medicago glycosyltransferase UGT71G1 reveals residues that control regioselectivity for (iso)flavonoid glycosylation. J Biol Chem 281:34441–34447
Jung W, Yu O, Lau S-M et al (2000) Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes. Nat Biotech 18:208–212
Kaul TN, Middleton E Jr, Ogra PL (1985) Antiviral effect of flavonoids on human viruses. J Med Virol 15:71–79
Kennedy JA, Matthews MA, Waterhouse AL (2000) Changes in grape seed polyphenols during fruit ripening. Phytochemistry 55:77–85
Kim BG, Kim SY, Song HS et al (2003) Cloning and expression of the isoflavone synthase gene (IFS-Tp) from Trifolium pratense. Mol Cells 15:301–306
Kitamura S, Shikazono N, Tanaka A (2004) TRANSPARENT TESTA 19 is involved in the accumulation of both anthocyanins and proanthocyanidins in Arabidopsis. Plant J 37:104–114
Kitaoka M, Kadokawa H, Sugano M et al (1998) Prenylflavonoids: a new class of non-steroidal phytoestrogen. 1. Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship. Planta Med 64:511–515
Kuzuyama T, Noel JP, Richard SB (2005) Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products. Nature 435:983–987
LaFlamme P, Khouri H, Gulick P et al (1993) Enzymatic prenylation of isoflavones in white lupin. Phytochemistry 34:147–151
Laughton MJ, Evans PJ, Moroney MA et al (1991) Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives: relationship to antioxidant activity and to iron ion-reducing ability. Biochem Pharmacol 42:1673–1681
Lee HP, Gourley L, Duffy SW et al (1991) Dietary effects on breast-cancer risk in Singapore. Lancet 337:1197–1200
Lee JM, Lee HK, Kim CY et al (2005) Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopis subjects. Br J Nutr 93:895–800
Lees GL (1992) Condensed tannins in some forage legumes: their role in the prevention of ruminant pasture bloat. Basic Life Sci 59:915–934
Li H, Flachowsky H, Fischer TC et al (2007) Maize Lc transcription factor enhances biosynthesis of anthocyanins, distinct proanthocyanidins and phenylpropanoids in apple (Malus domestica Borkh.). Planta 226:1243–1254
Li L, Modolo L, Escamilla-Trevino L et al (2007) Crystal structure of Medicago truncatula UGT85H2—insights into the structural basis of a multifunctional (iso)flavonoid glycosyltransferase. J Mol Biol 370:951–963
Lim EK, Ashford DA, Hou B, Jackson RG, Bowles DJ (2004) Arabidopsis glycosyltransferases as biocatalysts in fermentation for regioselective synthesis of diverse quercetin glucosides. Biotechnol Bioeng 87:623–631
Lin R, Li, T (1998) Effects of isoflavones on alcohol pharmacokinetics and alcohol-drinking behavior in rats. Am J Clin Nutr 68:1512S–1515S
Liu CJ, Blount JW, Steele CL et al (2002) Bottlenecks for metabolic engineering of isoflavone glycoconjugates in Arabidopsis. Proc Natl Acad Sci USA 99:14578–14583
Liu CJ, Deavours BE, Richard SB et al (2006) Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses. Plant Cell 18:3656–3669
Liu CJ, Dixon RA (2001) Elicitor-induced association of isoflavone O-methyltransferase with endomembranes prevents formation and 7-O-methylation of daidzein during isoflavonoid phytoalexin biosynthesis. Plant Cell 13:2643–2658
Liu CJ, Huhman DV, Sumner LW et al (2003) Regiospecific hydroxylation of isoflavones by cytochrome P450 81E enzymes from Medicago truncatula. Plant J 36:471–484
Liu R, Hu Y, Li J et al (2007) Production of soybean isoflavone genistein in non-legume plants via genetically modified secondary metabolism pathway. Metab Eng 9:1–7
Marinova K, Pourcel L, Weder B et al (2007) The Arabidopsis MATE transporter TT12 acts as a vacuolar flavonoid/H+-antiporter active in proanthocyanidin-accumulating cells of the seed coat. Plant Cell 19:2023–2038
Martens S, Forkmann G (1999) Cloning and expression of flavone synthease II from Gerbera hybrids. Plant J 20:611–618
Martin-Aragon S, Basabe B, Benedi JM et al (1999) In vitro and in vivo antioxidant properties of Vacinnum myrtillus. Pharm Biol 37:109–113
Middleton E, Kandaswami C (1992) Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol 43:1167–1179
Milligan S, Kalita J, Pocock V et al (2002) Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin. Reproduction (Cambridge) 123:235–242
Milligan SR, Kalita JC, Heyerick A et al (1999) Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 84:2249–2252
Milligan SR, Kalita JC, Pocock V et al (2000) The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab 85:4912–4915
Mizutani M, Tsuda S, Suzuki K et al (2003) Evaluation of post transcriptional gene silencing methods using flower color as the indicator. Plant Cell Physiol 44:s122
Modolo L, Blount JW, Achnine L et al (2007) A functional genomics approach to (iso)flavonoid glycosylation in the model legume Medicago truncatula. Plant Mol Biol 64:499–518
Nagashima S, Inagaki R, Kubo A et al (2004) cDNA cloning and expression of isoflavonoid-specific glucosyltransferase from Glycyrrhiza echinata cell-suspension cultures. Planta 218:456–459
Nakamura K, Akashi T, Aoki T et al (1999) Induction of isoflavonoid and retrochalcone branches of the flavonoid pathway in cultured Glycyrrhiza echinata cells treated with yeast extract. Biosci Biotechnol Biochem 63:1618–1620
Nesi N, Debeaujon I, Jond C et al (2000) The TT8 gene encodes a basic helix-loop-helix domain protein required for expression of DFR and BAN genes in Arabidopsis siliques. Plant Cell 12:1863–1878
Nesi N, Jond C, Debeaujon I et al (2001) The Arabidopsis TT2 gene encodes an R2R3 MYB domain protein that acts as a key determinant for proanthocyanidin accumulation in developing seed. Plant Cell 13:2099–2114
Offen W, Martinez-Fleites C, Yang M et al (2006) Structure of a flavonoid glucosyltransferase reveals the basis for plant natural product modification. EMBO J 25:1396–1405
Okura A, Arakawa H, Oka H et al (1988) Effect of genistein on topoisomerase activity and on the growth of [VAL 12]Ha-ras-transformed NIH 3T3 cells. Biochem Biophys Res Commun 157:183–189
Ono E, Fukuchi-Mizutani M, Nakamura N et al (2006) Yellow flowers generated by expression of the aurone biosynthetic pathway. Proc Natl Acad Sci USA 103:11075–11080
Pang Y, Peel GJ, Wright E et al (2007) Early steps in proanthocyanidin biosynthesis in the model legume Medicago truncatula. Plant Physiol (in press)
Paolocci F, Bovone T, Tosti N et al (2005) Light and an exogenous transcription factor qualitatively and quantitatively affect the biosynthetic pathway of condensed tannins in Lotus corniculatus leaves. J Exp Bot 56:1093–1103
Paolocci F, Robbins MP, Madeo L et al (2007) Ectopic expression of a basic helix-loop-helix gene transactivates parallel pathways of proanthocyanidin biosynthesis. Structure, expression, analysis, and genetic control of leucoanthocyanidin 4-reductase and anthocyanidin reductase genes in Lotus corniculatus. Plant Physiol 143:504–516
Pojer F, Wemakor E, Kammerer B et al (2003) CloQ, a prenyltransferase involved in clorobiocin biosynthesis. Proc Natl Acad Sci USA 100:2316–2321
Potter S, Baum J, Teng H et al (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68:1375S–1379S
Pourcel L, Routaboul JM, Kerhoas L et al (2005) TRANSPARENT TESTA10 encodes a laccase-like enzyme involved in oxidative polymerization of flavonoids in Arabidopsis seed coat. Plant Cell 17:2966–2980
Ray H, Yu M, Auser P et al (2003) Expression of anthocyanins and proanthocyanidins after transformation of alfalfa with maize Lc. Plant Physiol 132:1448–1463
Robbins MP, Paolocci F, Hughes J-W et al (2003) Sn, a maize bHLH gene, modulates anthocyanin and condensed tannin pathways in Lotus corniculatus. J Exp Bot 54:239–248
Ross JR, Li Y, Lim EK et al (2001) Higher plant glycosyltransferases. Genome Biol 2:3004.1–3004.6
Routaboul J-M, Kerhoas L, Debeaujon I et al (2006) Flavonoid diversity and biosynthesis in seed of Arabidopsis thaliana. Planta 224:96–107
Rufer CE, Kulling SE (2006) Antioxidant activity of isoflavones and their major metabolites using different in vitro assays. J Agric Food Chem 54:2926–2931
Sanchez MC, Cao G, Ou B et al (2003) Anthocyanin and proanthocyanidin content in selected white and red wines. Oxygen radical absorbance capacity compairson with nontraditional wines obtained from highbush blueberry. J Agric Food Chem 51:4889–4896
Sawada Y, Ayabe S (2005) Multiple mutagenesis of P450 isoflavonoid synthase reveals a key active-site residue. Biochem Biophy Res Commun 330:907–913
Sawada Y, Kinoshita K, Akashi T et al (2002) Key amino acid residues required for aryl migration catalysed by the cytochrome P450 2-hydroxyisoflavanone synthase. Plant J 31:555–564
Schopfer CR, Kochs G, Lottspeich F et al (1998) Molecular characterization and functional expression of dihydroxypterocarpan 6a-hydroxylase, an enzyme specific for pterocarpanoid phytoalexin biosynthesis in soybean (Glycine max L.). FEBS Lett 432:182–186
Serafini M, Bugianesi R, Maiani G et al (2003) Plasma antioxidants from chocolate. Nature 424:1013
Shao H, He X, Achnine L et al (2005) Crystal structures of a multifunctional triterpene/flavonoid glycosyltransferase from Medicago truncatula. Plant Cell 17:3141–3154
Sharma SB, Dixon RA (2006) Metabolic engineering of proanthocyanidins by ectopic expression of transcription factors in Arabidopsis thaliana. Plant J 44:62–75
Spencer JPE, Schroeter H, Kuhnle G et al (2001) Epicatechin and its in vivo metabolite, 3′-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase–3 activation. Biochem J 354:493–500
Sreevidya V, Srinivasa Rao C, Sullia S et al (2006) Metabolic engineering of rice with soybean isoflavone synthase for promoting nodulation gene expression in rhizobia. J Exp Bot 57:1957–1969
Steele CL, Gijzen M, Qutob D et al (1999) Molecular characterization of the enzyme catalyzing the aryl migration reaction of isoflavonoid biosynthesis in soybean. Arch Biochem Biophys 367:147–150
Strauss L, Santti R, Saarinen N et al (1998) Dietary phytoestrogens and their role in hormonally dependent disease. Toxicol Lett 103:349–354
Sweeney MT, Thomson MJ, Pfeil BE et al (2006) Caught red-handed: Rc encodes a basic helix-loop-helix protein conditioning red pericarp in rice. Plant Cell 18:283–294
Tahara S, Ibrahim RK (1995) Prenylated isoflavonoids—an update. Phytochemistry 38:1073–1094
Tanaka Y, Tsuda S, Kusumi T (1998) Metabolic engineering to modify flower color. Plant Cell Physiol 39:1119–1126
Tanner GJ, Francki KT, Abrahams S et al (2003) Proanthocyanidin biosynthesis in plants. Purification of legume leucoanthocyanidin reductase and molecular cloning of its cDNA. J Biol Chem 278:31647–31656
Tian L, Dixon RA (2006) Engineering isoflavone metabolism with an artificial bifunctional enzyme. Planta 224:496–507
Tikkanen MJ, Adlercreutz H (2000) Dietary soy-derived isoflavone phytoestrogens: could they have a role in coronary heart disease prevention. Biochem Pharmacol 60:1–5
Tohge T, Nishiyama Y, Hirai MY et al (2005) Functional genomics by integrated analysis of metabolome and transcriptome of Arabidopsis plants over-expressing an MYB transcription factor. Plant J 42:218–235
Turnbull JJ, Nakajima J, Welford RD et al (2004) Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis. J Biol Chem 279:1206–1216
Vinson JA, Mandarano MA, Shuta DL et al (2002) Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster aterosclerosis model. Mol Cell Biochem 240:99–103
Walker AR, Davison PA, Bolognesi-Winfield AC et al (1999) The TRANSPARENT TESTA GLABRA 1 locus, which regulates trichome differentiation and anthocyanin biosynthesis in Arabidopsis, encodes a WD40 repeat protein. Plant Cell 11:1377–1349
Wallace JW, Grisebach H (1973) The in vivo incorporation of a flavanone into C-glycosylflavones. Biochim Biophys Acta 304:837–841
Wallace JW, Mabry TJ, Alston RE (1969) On the biogenesis of flavone O-glycosides and C-glycosides in the lemnaceae. Phytochemistry 8:93–99
Welle R, Grisebach H (1988) Induction of phytoalexin synthesis in soybean: enzymatic cyclization of prenylated pterocarpans to glyceollin isomers. Arch Biochem Biophys 263:191–198
Welle R, Grisebach H (1991) Properties and solubilization of the prenyltransferase of isoflavonoid phytoalexin biosynthesis in soybean. Phytochemistry 30:479–484
Wiseman H, OReilly JD, Adlercreutz H et al (2000) Isoflavone phytoestrogens consumed in soy decrease F-2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr 72:395–400
Wu Q, Presig CL, VanEtten HD (1997) Isolation of the cDNAs encoding (+)6a-hydroxymaackiain 3-O-methyltransferase, the terminal step for the synthesis of the phytoalexin pisatin in Pisum satium. Plant Mol Biol 35:551–560
Xie D, Sharma SR, Paiva NL et al (2003) Role of anthocyanidin reductase, encoded by BANYULS in plant flavonoid biosynthesis. Science 299:396–399
Xie DY, Sharma SB, Dixon RA (2004) Anthocyanidin reductases from Medicago truncatula and Arabidopsis thaliana. Arch Biochem Biophys 422:91–102
Xie DY, Sharma B, Wright E et al (2006) Metabolic engineering of proanthocyanidins through co-expression of anthocyanidin reductase and the PAP1 MYB transcription factor. Plant J 45:895–907
Yu O, Jung W, Shi J et al (2000) Production of the isoflavones genistein and daidzein in non-legume dicot and monocot tissues. Plant Physiol 124:781–794
Yu O, Shi J, Hession AO et al (2003) Metabolic engineering to increase isoflavone biosynthesis in soybean seed. Phytochemistry 63:753–763
Zhan AQ, Zhu QY, Luk YS et al (1997) Inhibitory effects of jasmine green tea epicatechin isomers on free radical-induced lysis of red blood cells. Life Sci 61:383–394
Zhang F, Gonzalez A, Zhao M et al (2003) A network of redundant bHLH proteins functions in all TTG1-dependent pathways of Arabidopsis. Development 130:4859–4869
Zhang S, Chen S, Shen Y et al (2006) Puerarin induces angiogenesis in myocardium of rat with myocardial infarction. Biol Pharm Bull 29:945–950
Zubieta C, Dixon RA, Noel JP (2001) Crystal structures of chalcone O-methyltransferase and isoflavone O-methyltransferase reveal the structural basis for substrate specificity in plant O-methyltransferases. Nat Struct Biol 8:271–279
Zuker A, Tzfira T, Ben-Meir H et al (2002) Modification of flower color and fragrance by antisense suppression of the flavanone 3-hydroxylase gene. Mol Breed 9:33–41
Zuurbier KWM, Fung SY, Scheffer JJC et al (1998) In-vitro prenylation of aromatic intermediates in the biosynthesis of bitter acids in Humulus lupulus. Phytochemistry 49:2315–2322
Acknowledgements
We thank Dr. Gregory Peel for critical reading of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tian, L., Pang, Y. & Dixon, R.A. Biosynthesis and genetic engineering of proanthocyanidins and (iso)flavonoids. Phytochem Rev 7, 445–465 (2008). https://doi.org/10.1007/s11101-007-9076-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11101-007-9076-y