Resveratrol synthase

Not direct gene produa however, gene for enzyme (resveratrol synthase) catalyzing synthesis of stilbene phytoalexin in peanut has been cloned. 

Resveratrol-3-O-p-D-glucoside is called piceid. Resveratrol is a naturally occurring phytoalexin ( defender of the plant ) which is produced in response to an injury, such as mechanical trauma, ultraviolet light, and infection by pathogenic microorganisms, especially fungi, providing means for defense [Bertelli et al., 1995 Baolin et al., 2004 Bak et al., 2006 Baur et al., 2006]. It is formed via a condensation reaction between three molecules of malonyl CoA and one molecule of 4-coumaroyl CoA [Soleas et al., 1997], Resveratrol synthase facilitates this condensation reaction, which also produces four... 

Schubert R, Fischer R, Hain R, Schreier PH, Bahnweg G, Ernst D, Sandermann HJr. 1997. An ozone-responsive region of the grapevine resveratrol synthase promoter differs from the basal pathogen-responsive sequence. Plant Mol Biol 34 417-426. 

The biosynthesis of the stilbenoids, including 1, has been previously reviewed. Briefly, the synthesis of 1 is dependent upon a single key enzyme known as stilbene synthase or resveratrol synthase as part of a mixed phenylpropanoid-polyketide pathway [2,3,4,5,6] (Fig. (1)). Stilbene synthase catalyzes the formation of 1 through the condensation of one p-coumaroyl CoA and three malonyl CoA molecules, both of which are ubiquitous intermediary plant metabolites. 

Lim JD, Yun SJ, Chung IM, Yu CY (2005) Resveratrol synthase transgene expression and accumulation of resveratrol glycoside in Rehmannia glutinosa. Mol Breed 16 219-233... 

Addition. Resveratrol. The biosynthetic pathway to resveratrol diverges from the flavonoid pathway after the third malonyl-CoA condensation. Cyclization of the common polyketide intermediate catalyzed by resveratrol synthase yields the stilbene derivative resveratrol, whereas the same intermediate catalyzed by chal-cone synthase yields the common flavonoid precursor chalcone (Fig. 6.8). Resveratrol, well known as a functional food ingredient (e.g., grape skin, red wine) with strong antioxidant properties (cardiovascular protection), and its 3-glucopyranoside piceid turned out to be also present in the skin of tomato fruits, S. lycopersicum (Ragab et al. 2006). 

Schroder, G., Brown, J.W.S. and Schroder, J. (1988) Molecular analysis of resveratrol synthase cDNA genomic clones and relationship with chalcone synthase. Eur. J. Biochem., 172,161-169. 

To resolve the issue of cyclization specificity, the x-ray crystal structure of the stilbene synthase from pine was determined to atomic resolution. This information allowed the mutagenic conversion of alfalfa CHS to a functional STS, and crystal structures of this engineered STS were solved, in the apo form and with resveratrol bound in the active site (Austin and Noel, unpublished). These experiments support a mechanistic proposal, which prompted further mutagenic and modeling experiments. This work has allowed the elucidation of the structural and mechanistic basis for cyclization specificity (aldol versus Claisen condensation) in the CHS family of type III PKSs. 

LANZ T., TROPF, S., MARNER, F.J, SCHRODER, J., SCHRODER, G., The role of cysteines in polyketide synthases site-directed mutagenesis of resveratrol and chalcone synthases, two key enzymes in different plant-specific pathways, J. Biol. Chem., 1991, 266, 9971-9976. 

PKSs are characterized by their ability to catalyze the formation of polyketide chains from the sequential condensation of acetate units from malonate thioesters. In plants they produce a range of natural products with varied in vivo and pharmacological properties. PKSs of particular note include acridone synthase, bibenzyl synthase, 2-pyrone synthase, and stilbene synthase (STS). STS forms resveratrol, a plant defense compound of much interest with regard to human health. STS shares high sequence identity with CHS, and is considered to have evolved from CHS more than once. ° Knowledge of the molecular structure of the CHS-like enzymes has allowed direct engineering of CHS and STS to alter their catalytic activities, including the number of condensations carried out (reviewed in Refs. 46, 51, 52). These reviews also present extensive, and superbly illustrated, discussions of CHS enzyme structure and reaction mechanism. 

Wallerath, T., Deckert, G., Temes, T., Anderson, H., Li, H., Witte, K., and Forstermann, U., Resveratrol, a polyphenolic ph54oalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation, 106, 1652, 2002. 

Chan MM, Mattiacci JA, Hwang HS, Shah A, Fong D. 2000. Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem Pharmacol 60 1539-1548. 

Hain R, Bieseler B, Kindi H, Schroder G, Stocker R. 1990 Expression of a stilbene synthase gene in Nicotiana tabacum results in synthesis of the phytoalexin resveratrol. Plant Mol Biol 15 325-335. 

Tsai SH, Lin-Shiau SY, Lin JK. 1999. Suppression of nitric oxide synthase and the down-regulation of the activation of NF-kB in macrophages by resveratrol. Br J Pharmacol 126 673-680. 

Borie B, Jeandet P, Parize A, Bessis R, Adrian M. 2004. Resveratrol and stylbene synthase mRNA production in grapevine leaves treated with biotic and abiotic phytoalexin elicitors. Am J Enol Vitic 55 160-164. 

Hsieh, T.C., Juan, G.L., Darzynkiewicz, Z., and Wu, J.M., Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21 wafi/cipi suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and Gj, Cancer Res., 59, 2596, 1999. 

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