Resveratrol biosynthesis

Halls C, Yu O. 2008. Potential for metabolic engineering of resveratrol biosynthesis. Trends Biotech 26 77-81. 

Zhang Y, Li S-Z, Pan X, Cahoon RE, Jaworski JG, Wang X, Jez JM, Chen F, Yu O. 2006. Using unnatural protein fusion to engineer resveratrol biosynthesis in yeast and mammalian cells. J Am Chem Soc 128 13030-13031. 

Wang Y, Halls C, Zhang J, Matsuno M, Zhang Y, Yu O (2011) Stepwise increase of resveratrol biosynthesis in yeast Saccharomyces cerevisiae by metabolic engineering. Metab Eng 13 455 3... 

Remarkably, the extracts of transgenic resveratrol containing tomato fruits displayed an anti-inflammatory effect greater than that of chemically synthesized resveratrol. In conclusion, these results indicate that the presence of a new biosynthetic route responsible for resveratrol biosynthesis improves the health-giving biological activities of tomatoes. 

Giovinazzo G, Ingrosso I, Paradiso A, De Gara L, Santino A (2012) Resveratrol biosynthesis plant metabolic engineering for nutritional improvement of food. Plant Foods Hum Nutr. doi 10.1007/sl 1130-012-0299-8 [Epub ahead of print]... 

Resveratrol biosynthesis branches from the phenylpropanoid pathway. The resveratrol biosynthesis pathway consists of four enzymesrphenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H), 4-coumarate CoA ligase (4CL), and stilbene synthase (STS). The first two enzymes of the pathway, PAL and C4H, convert phenylalanine into /)-coumaric acid. The third enzyme, 4CL, attaches /)-coumaric acid to the pantetheine group of coenzyme-A (CoA) to produce 4-coumaroyl-CoA. The fourth enzyme, STS, catalyzes the condensation of resveratrol from one molecule of 4-coumaroyl-CoA and three molecules of malonyl-CoA, which originate from fatty acid biosynthesis. TAL is homologous to PAL and converts the amino acid tyrosine directly into / -coumaric acid. Methylated resveratrol derivatives of pinostilbene and pterostilbene are produced by resveratrol O-methyltransferase (ROMT) from resveratrol [135] (Figure 10.10). 

Wang, Y., Halls, C., Zhang, Matsuno, M., Zhang, Y. et al. (2011) Stepwise increase of resveratrol biosynthesis... 

Wang, Y. and Yu, O. (2012) Synthetic scaffolds increased resveratrol biosynthesis in engineered yeast cells. J. Biotechnol, 157, 258—260. 

Iriti M, Rossoni M, Borgo M, Faoro F. 2004. Benzothiadiazole enhances resveratrol and anthocyanin biosynthesis in grapevine, meanwhile improving resistance to Botrytis cinerea. J Agric Food Chem 52 4406-4413. 

Ulrich S, Huwiler A, Loitsch S, Schmidt H, Stein JM. 2007. De novo ceramide biosynthesis is associated with resveratrol-induced inhibition of ornithine decarboxylase activity. Biochem Pharmacol 74 281-289. 

Resveratrol shows a direct inhibitory activity on heart fibroblasts and suppresses the spreading of heart fibrose (05MI1131). The vasoconstrictor peptide endothelin (ET-1) is controlled in its biosynthesis by polyphenols, and especially by resveratrol. Only 5 pmol causes an endothelin-depen-dent vasodilatation and lowers blood pressure (88NAT411, 01MI152, 01NAT863,06NAT566). 

Gebhardt, R. and Beck, H. 1996. Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte culture. Lipids 31, 1269-1276. Gehm, B.D., McAndrews, J.M., Chien, P.Y., and Jameson, J.L. 1997. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for estrogen receptor. Proc. Natl Acad. Sci. 94, 14138-14143. 

Stilbenes can also occur in oligomeric and polymeric forms, so-called viniferins. They are induced by oxidative polymerization of the monomer resveratrol through the activity of a peroxidase (Jean-Denis et al. 2006). Figure 9C.7 shows the biosynthesis of trans-s-mmfcxm. 

The oxidation of resveratrol (1) by the COX-1 peroxidase led to the formation of two major products namely cw-e-viniferin (447) and trans-i/-viniferin. Identity of these viniferins was established by HPLC and LC/UV/MS, and the mechanism of viniferin formation from resveratrol (1) was investigated [257]. Combined with the work of Niwa et al, we conclude the plausible biosynthesis of stilbeneoligomers in the Vitaceae family is fairly clear (see Schemes 1 and 2). 

Li D, Dammer EB, Sewer MB (2012) Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc. Endocrinology 153(7) 3258-3268... 

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