Flavonols biosynthesis

Tudela JA, Cantos E, Esprn JC, Tomas-Barberan FA and Gil MI. 2002. Induction of antioxidant flavonol biosynthesis in fresh-cut potatoes. Effect of domestic cooking. J Agric Food Chem 50(21) 5925-5931. 

Approximately 1030 flavonols are known (Harbome, 1991). Most of these are glycosides derived from approximately 300 flavonoid aglycones. Flavonol biosynthesis probably occurs via a 2-hydroxy intermediate with subsequent dehydration, in a manner similar to that proposed for formation of flavones. Flavonol formation with extracts from flowers of Matthiola and Petunia requires a soluble 2-oxo-glutarate-dependent dioxygenase (Heller and Forkmann, 1988). 

Flavanones are widely distributed (at least 60 families) but they are accumulated in few plants (Bohm, 1982, 1988). These flavonoids have a center of asymmetry at C-2 (see earlier discussion under flavone and flavonol biosynthesis). The absolute configuration of a number of these compounds has been established. Dihydroflavonols, or 3-hydroxyflava-nones, that have two asymmetric carbons, C-2 and C-3, also are intermediates in the synthesis of several major types of flavonoids such as flavonols and anthocyanins (see above). Although the majority of dihydroflavonols possess (2/ ,3/ )-stereochemistry, compounds with (25,35)-stereochemistry are known. 

Plant metabolic engineering has provided a means to improve polyphenol composition and levels. For example, tomato plants with enhanced flavonols have been recently developed through the overexpression of a transcription factor able to activate flavonol biosynthesis [30-32]. 

Scheme 59.1 Schematic of the major branch pathways of flavone and flavonol biosynthesis...

Figure 5.4. Abbreviated scheme for biosynthesis of major flavonoid subclasses, showing the primary enzymes and substrates leading to different subclasses. Bold-faced, uppercase abbreviations refer to enzyme names, whereas substrate names are presented in lowercase letters. PAL, phenylalanine ammonia lyase C4H, cinnamate 4-hydroxylase 4CL, 4-coumarate CoA ligase CHS, chalcone synthase CHI, chalcone isomerase CHR, chalcone reductase IPS, isoflavone synthase F3H, flavonone 3-hydroxylase F3 H, flavonoid 3 -hydroxylase F3 5 H, flavonoid 3 5 -hydroxylase FNSI/II, flavone synthase DFR, dihydroflavonol 4-reductase FLS, flavonol synthase ANS, anthocyanidin synthase LAR, leucoanthocyanidin reductase ANR, anthocyanidin reductase UFGT, UDP-glucose flavonoid 3-O-glucosyltransferase. R3 = H or OH. R5 = H or OH. Glc = glucose. Please refer to text for more information.

Turnbull JJ, Nakajima J, Welford RW, Yamazaki M, Saito K and Schofield CJ. 2004. Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis anthocyanidin synthase, flavonol synthase, and flavanone 33-hydroxylase. J Biol Chem 279 1206-1216. 

Flavonol synthase (FLS E.C.l.14.11.23) catalyzes the committed step in the production of fiavonols by introduction of a double bond between C2 and C3 of the corresponding dihydroflavonols. Like E3H, ELS has been described as a 2-oxoglutatarate-dependent dioxygenase based on its cofactor requirements for 2-oxoglutarate, Fe, and ascorbate. FLS was initially identified in enzyme preparations from illuminated parsley cell suspension cultures [67]. Subsequently, FLS was characterized from the flower buds of Matthiola incana and carnation (Dianthus caryophyllus L.), and it was suggested that there was regulation between flavonol and anthocyanidin biosynthesis [83, 84]. 

Stitch K, Eidenberger T, Wurst F, Forkmann G (1992) Flavonol synthase activity and the regulation of flavonol and anthocyanin biosynthesis during flower development in Dianthus caryophyllus. Z Naturforsch 47C 553-560... 

Jourdan PS, Mansell RL (1982) Isolation and partial characterization of three glucosyl transferases involved in the biosynthesis of flavonol tiiglucosides in Pisum sativum L. Arch Biochem Biophys 213 434-443... 

Regulation of Flavonoid Synthesis in C. americanum. Biosynthesis of methylated flavonol glucosides seems to be under tight regulation, not only by the substrate specificity of the enzymes involved, but also by other factors, among which are (a) the strict position specificity of these enzymes towards their hydroxylated or partially methylated substrates (b) the apparent difference in microenvironment of the different methyl-transferases, whereby those earlier in the pathway utilized aglycones whereas later enzymes accepted only glucosides as substrates (c) the subtle characteristic differences in methyl-transferases with respect to their pH optima, pi values and requirement for Mg ions, despite their similar molecular size ... 

The key enzymes involved in the formation of the hydroxycinnamic acids (HCAs) from phenylalanine and malonyl-CoA are now discussed in detail, while later sections address the branches of the flavonoid pathway leading to anthocyanins, aurones, flavones, flavonols, PAs, and isotlavonoids. This is followed by brief reviews of the regulation of flavonoid biosynthesis and the use of flavonoid genes in plant biotechnology. To assist the reader. Figure 3.1 presents the carbon numbering for the various flavonoid types discussed. 

Flavonol synthesis occurs in two main periods the first one around flowering and the second after the main period of anthocyanin biosynthesis. In the latter phase, flavonol accumulation is highly dependent on environmental factors and, in particular, much increased by sun exposure of the berries. ... 

Biogenetically, chalcones are the immediate precursors of flavanones, and some flavanones isomerize by ring opening into chalcones during isolation from plants or after chemical treatment with alkali. In turn, flavanones are intermediates in the biosynthesis of most other flavonoid groups, including flavones, flavonols, and isoflavonoids. For more information on the biosynthesis of flavonoids and flavanones in particular, the reader is referred to Chapter 3 and reviews by Heller and Forkmann. ... 

Proanthocyanidins and Procyanidins - In a classical study Bate-Smith ( ) used the patterns of distribution of the three principal classes of phenolic metabolites, which are found in the leaves of plants, as a basis for classification. The biosynthesis of these phenols - (i) proanthocyanidins (ii) glycosylated flavonols and (iii) hydroxycinnamoyl esters - is believed to be associated with the development in plants of the capacity to synthesise the structural polymer lignin by the diversion from protein synthesis of the amino-acids L-phenylalanine and L-tyro-sine. Vascular plants thus employ one or more of the p-hydroxy-cinnarayl alcohols (2,3, and 4), which are derived by enzymic reduction (NADH) of the coenzyme A esters of the corresponding hydroxycinnamic acids, as precursors to lignin. The same coenzyme A esters also form the points of biosynthetic departure for the three groups of phenolic metabolites (i, ii, iii), Figure 1. 

---