Browse > Article
http://dx.doi.org/10.5010/JPB.2002.29.4.265

Flavonoid Biosynthesis: Biochemistry and Metabolic Engineering  

Park, Jong-Sug (Metabolic Engineering Division, National Institute of Agricultural Biotechnology, RDA)
Kim, Jong-Bum (Metabolic Engineering Division, National Institute of Agricultural Biotechnology, RDA)
Kim, Kyung-Hwan (Metabolic Engineering Division, National Institute of Agricultural Biotechnology, RDA)
Ha, Sun-Hwa (Metabolic Engineering Division, National Institute of Agricultural Biotechnology, RDA)
Han, Bum-Soo (Metabolic Engineering Division, National Institute of Agricultural Biotechnology, RDA)
Kim, Yong-Hwan (Metabolic Engineering Division, National Institute of Agricultural Biotechnology, RDA)
Publication Information
Journal of Plant Biotechnology / v.29, no.4, 2002 , pp. 265-275 More about this Journal
Abstract
Flavonoid biosynthesis is one of the most extensively studied areas in the secondary metabolism. Due to the study of flavonoid metabolism in diverse plant system, the pathways become the best characterized secondary metabolites and can be excellent targets for metabolic engineering. These flavonoid-derived secondary metabolites have been considerably divergent functional roles: floral pigment, anticancer, antiviral, antitoxin, and hepatoprotective. Three species have been significant for elucidating the flavonoid metabolism and isolating the genes controlling the flavonoid genes: maize (Zea mays), snapdragon (Antirrhinum majus) and petunia (Prtunia hybrida). Recently, many genes involved in biosynthesis of flavonoid have been isolated and characterized using mutation and recombinant DNA technologies including transposon tagging and T-DNA tagging which are novel approaches for the discovery of uncharacterized genes. Metabolic engineering of flavonoid biosynthesis was approached by sense or antisense manipulation of the genes related with flavonoid pathway, or by modified expression of regulatory genes. So, the use of a variety of experimental tools and metabolic engineering facilitated the characterization of the flavonoid metabolism. Here we review recent progresses in flavonoid metabolism: confirmation of genes, metabolic engineering, and applications in the industrial use.
Keywords
Flavonoid biosynthesis; metabolic engineering;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Beld M, Martin C, Huits H, Stuithe AR, Gerats AGM (1989) Flavonoid synthesis in Petunia hybrida: Partial characterization of dihydroflavonol-4-reductase genes. Plant Mol Biol 13:491-502   DOI   ScienceOn
2 Borevitz JO, Xia Y, Blount J, Dixon RA, Lamb C (2000) Activation tagging identifies a conserved MYB regulatory of phenylpropanoid biosynthesis. Plant Cell 12:2383-2393   DOI   ScienceOn
3 Britsch L, Ruhnau-Brich B, Forkmann G (1992) Molecular cloning, sequence analysis, and in vitro expression of flavanone 3 beta-hydroxylase from Petunia hybrida. J Biol Chem 267:5380-5387
4 Davies K, Bloor S, Spiller G (1998) Production of yellow colour in flower: redirection of flavonoid biosynthesis in Petunia. Plant J 13:259-266   DOI   ScienceOn
5 de Vetten N, ter Horst J, van Schaik J-P, de Boer A, Mol J, Koes R (1999) A cytochrome b5 is required for full activity of flavonoid 3'5'-hydroxylase, a cytochrome P450 involved in the formation of blue flower. Proc Natl Acad Sci USA 96:778-783   DOI
6 de Vetten N, Quattrocchio F, Mol J, Koes R (1997) The an11 locus controlling flower pigmentation in petunia encodes a novel WD-repeat protein conserved in yeast, Plants and animals. Genes Dev 11:1422-1434   DOI   ScienceOn
7 Elomaa P, Holton T (1994) Modification of flower colour using genetic engineering. Biotechnol Eng Rev 12:63-88   DOI   ScienceOn
8 Akashi R, Fukuchimizutani M, Aoki T, Ueyama Y, Ayabe S (1999) Molecular cloning and biochemical characterization of novel cytochrome P450, flavone synthase II, that catalyses direct conversion of flavanones to flavones. Plant Cell Physiol 40:1182-1186   DOI   ScienceOn
9 Dooner HK, Robbins TP, Jorgensen RA (1991) Genetic and developmental control of anthocyanin biosynthesis. Annu Rev Genet 25:173-199   DOI   ScienceOn
10 Dooner HK, Weck E, Adams S, Ralston E, Favreau M, English J (1985) A molecular genetic analysis of insertions in the bronze locus in maize. Mol Gen Genet 200:240-246   DOI
11 Federoff NV, Furtek DB, Nelson OE (1984) Cloning of the bronze locus in maize by a simple and generalizable procedure using the transposable element Activator. Proc Natl Acad Sci ISA 81:3825-3829   DOI   ScienceOn
12 Brugliera F, Barri-Rewe G, Holton TA, Mason JG (1999) Isolation and characterization of a flavonoid 3'-hydroxylase cDNA clone corresponding to the Htl locus of Petunia hybrida. 19:441-451
13 Damiani F, Paolocd F, Cluster P, Arcioni S, Tanner G, Joseph R, Li Y, de Majnik J, Larkin P (1999) The maize transcription factor Sn alters proanthocyanidin synthesis in transgenic Lotus corniculatus plants. Aust J Plant Physiol 26:159-169   DOI   ScienceOn
14 Brugliera F, Tull D, Holton TA, Karan M, Treloar N, Simpson K, Skurozynska J, Nason JG (2000) Introduction of a cytochrome b5 enhances the activity of flavonoid 3'5' (cytochrome P450) in transgenic carnation. Sixth International Congress of Plant Molecular Biology. University of Laval, Quebec, pp 6-8
15 Coen EC, Carpenter R, Martin C (1986) Transposable elements generate novel spatial patterns of gene expression in Antirrhinum Majus. Cell 47:285-296   DOI   ScienceOn
16 Cone KC, Burr FA, Burr B (1986) Molecular analysis of the maize anthocyanin regulatory locus C1. Proc Natl Acad Sci USA 83:9631-9635   DOI   ScienceOn
17 Jung W, Yu O, Lau S, Keefe D, Odell J, Fader G, Mc Gonigle B (2000) Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isolfavones in legumes. Nat Biotechnol 18:208-212   DOI   ScienceOn
18 Koes R, De Vetten N, Mol J (2000) Cytochrome $b_{5}$ form Petunia. PCT-international Patent Application No. WO 00/09720
19 Kreuzaler F, Ragg H, Fautz E, Kuhn DN, Hahlbrock K (1983) UV-induction of chalcone synthase mRNA in cell suspension cultures of Petrosetinum hortense. Proc Natl Acad Sci USA 80:2591-2593   DOI   ScienceOn
20 Larson, RL and Bussard JB (1986) Microsomal flavonoid 3'-monooxygenase from maize seedlings. Plant Physiol 86:483-486
21 Dixon RA (1999) Isoflavonoid: biochemistry, molecular biology, and biological functions, in Comprehensive Natural Products Chemistry (Vol. 1). (Sankawa, U. ed) pp 773-823
22 de Vos R, Bovy A, Busink H, Muir S, Collins G, Verhoeyen M (2000) Improving health potential of crop plants by means of flavonoid pathway engineering. Polyphenols Cummun 1:25-26
23 Debeaujon I, Peeters AJM, Leon-Kloosterziel KM, Koornneef M (2001) The TRANSPARENT TESTA12 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   DOI   ScienceOn
24 Devic M, Guilleminot J, Debeaujon I, Bechtold N, Bensaude E, Koornneef M, Pelletier G, Delseny M (1999) The BANTULS gene encodes a DFR-like protein and is a marker of earley seed coat development. Plant J 19:387-398   DOI   ScienceOn
25 Dixon RA, Steele CL (1999) Flavonoids and isoflavonoid - a gold mine for metabolic engineering. Trends Plant Sci 4:394-400   DOI   ScienceOn
26 Meyer P, Heidmann I, Forkmann G, Saedler H (1987) A new Petunia flower colour generated by transformation of a mutant with a maize gene. Nature 330:667-678   DOI   ScienceOn
27 Mol J, Grotewold E, Koes R (1998) How genes paint flowers and seeds. Trends Plant Sci 3:212-217   DOI   ScienceOn
28 Muir SR, Collins GJ, Robinson S, Hughes S, Bovy A, De Vos CHR, van Tunen AJ, Verhoeyen ME (2001) Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols. Nat Biotechnol 19:470-474   DOI   ScienceOn
29 Forkmann G, Ruhhau B (1987) Distinct substrate specificity of dihydroflavonol 4-reductase from flowers of Petunia hybrida. Z Naturforsch C 42:1146-1148
30 Forkmann G, Martens S (2001) Metabolic engineering and applications of flavonoids. Curr Opin in Biotech 12:155-160   DOI   ScienceOn
31 Goodrich J, Carpenter R, Coen ES (1992) A common gene regulates pigmentation pattern in diverse plant species. Cell 68:955-964   DOI   ScienceOn
32 Holton TA, Brugliera F, Lester DR, Tanaka Y, Hyland CD, Melting JGT, Lu C-Y, Farcy E, Stevenson TW, Cornish EC (1993) Cloning and expression of cytochrome P450 genes controlling flower colour. Nature 366:276-279   DOI   ScienceOn
33 Holton TA, Cornish EC (1995) Genetics and biochemistry of anthocyanin biosynthesis. Plant Cell 7:1071-1083   DOI   ScienceOn
34 Johnson CS, Kolevski B, Smyth DR (2002) TRANSPARENT TESTA GLABTA2, a trichome and seed coat development gene of Arabidopsis, encodes a WRKY transcription factor. Plant Cell 14:1359-1375   DOI   ScienceOn
35 Steele CL, Gijzen M, Qutob D, Dixon RA (1999) Molecular characterization of the enzyme catalyzing the acyl migration reaction of isoflavonoid biosynthesis in soybean. Arch Biochem Biophys 367:146-150   DOI   ScienceOn
36 Stich K, Edenberger T, Wurst F, Forkmann G (1992) Enzymatic conversion of dihydroflavonols to f1avan-3,4-diols using flower extracts of Dian.thus caryophyttus L. (carnation). Planta 187: 103-108
37 Lechelt C, Peterson T, Laird A, Chen J, Dellaporta SL, Dennis E, Peacock WJ, Starlinger P (1989) Isolation and molecular analysis ofthe maize Plocus. Mol Gen Genet 219:225-234
38 Martin C, Prescott A, Mackay S, Bartlett J, Vrijlandt E (1991) Control of anthocyanin biosynthesis in flowers of Antirrhinum majus.Plant J 1:37-49   DOI   ScienceOn
39 Ludwig SR, Habera LF, Dellaporta SL, Wessler SR (1989) Lc, a member of the maize R gene family responsible for tissue-specific anthocyanin production, encodes a protein similar to transcriptional activators and contains the myc-homology region. Proc Natl Acad Sci USA 86:7092-7096   DOI   ScienceOn
40 Martens S, Forkmann G (1999) Cloning and expression of flavone synthase II from Gerbera hybiids. Plant J 20:611-618   DOI   ScienceOn
41 Mehdy MC, Lamb CJ (1987) Chalcone isomerase cDNA cloning and mRNA induction by fungal elicitor, wounding and infection. EMBO J 6:1527-1533
42 Menssen A, Hohmann S, Martin W, Schnable PS, Peterson PA, Saedler H, Gierl A (1990) The En/Spm transposable element of Zea mays contains splice sites at the termini generating a novel intron from a dSpm element in the A2 gene. EMBO J 9:3051-3057
43 Yu O, Jung W, Shi J, Croes RA, Fader GM, McGonigle B, Odell JT (2000) Production of the isoflavones genistein and daidzein in non-legume dicot and monocot tissues. Plant Physiol 124:781-793   DOI   ScienceOn
44 Nesi N, Debeaujon I, Jond C, Pelletier G, Caboche M, Lepiniec L (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   DOI   ScienceOn
45 Setchell K (1998) Phytoestrogens: The biochemistry, Physiology and implication for human health of soy isoflavones. Am J Clin Nutr 68:1333S-1346S   DOI
46 Quattrocchio F, Wing J, van der Woude K, Souer E, de Vetter N, Mol J, Koes R (1999) Molecular analysis of the anthocyanin 2 gene of petunia and its role in the evolution of flower color. Plant Cell 11:1433-1444   DOI   ScienceOn
47 Reddy AR, Britsch L, Salamini F, Saelder H, Rohde W (1987) The A1 (Anthocyanin-1) locus in Zea mays encodes dihydroquercetin reductase. Plant Sci 52:7-13   DOI   ScienceOn
48 Robbins M, Bavage A, Strudwicke C, Morris P (1998) Genetic manipulation of condensed tannins in higher plants. Plant Physiol 116:1133-1144   DOI   ScienceOn
49 Setchell K, Cassidy A (1999) Dietary isoflavones: biological effects and relevance to human health. J Nut 129:758S-767S   DOI
50 Spelt C, Quattrocchio F, Mol JNM, Koes R (2000) Anthocyanin 1 of petunia encodes a basic helix-loop-helix protein that directly activates transcription of structural anthocyanin genes. Plant Cell 12:1619-1631   DOI   ScienceOn
51 Tanaka Y, Tsuda S, Kusumi T (1998) Metabolic engineering to modify flower colour. Plant Cell Physiol 39:1119-1126   DOI   ScienceOn
52 Vainstein A, Zuker A, Ovadis M (2000) Transgenic plants and method for transforming carnations. PCT-International Patent Application No. WO 00/50613
53 van Tunen AJ, Hartman SA, Mur LA, Mol JNM (1989) Regulation of chalcone isomerase (CHI) gene expression in Petunia hybrida. The use of alternative promoters in corolla, anthers and pollen. Plan Mol Biol 12:539-551   DOI   ScienceOn
54 Mnkel-Shirley B (2001) Flavonoid biosynthesis: a colorful model for genetics, biochemistry, cell biology, and biotechnology. Plant Physiol 126:485-493   DOI   ScienceOn
55 van Tunen AJ, Koes RE, Spelt CE, van der Krol AR, Stuitje AR, Mol JNM (1988) Cloning of the two chalcone flavanone isomerase genes form Petunia hybrida: Coordinate, lightregulated and differential expression of flavonoid genes. EMBO J 4:1257-1263
56 Walker AR, Davison PA, Bolognesi-Winfield AC, James CM, Siinivasan N, Blundell TL, Esch JJ, Marks MD, Gray JC (1999) The TRANSPARENT TESTA GLABRA 1 locus, which regulates trichome differentiation and anthocyanin biosynthesis in Arabidopsis, encodes a WD40 repeat protein. Plant Cell 11:1257-1263   DOI   ScienceOn
57 Weisshaar B, Armstrong GA, Block A, da Costa e Silva O, Hahlbrock K (1991) Light-inducible and constitutively expressed DNA-binding proteins recognizing a plant promotor element with functional relevance in light responsiveness. EMBO J 10:1777-1786