Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol

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dc.contributor.authorBecker J.V.W.
dc.contributor.authorArmstrong G.O.
dc.contributor.authorVan Der Merwe M.J.
dc.contributor.authorLambrechts M.G.
dc.contributor.authorVivier M.A.
dc.contributor.authorPretorius I.S.
dc.date.accessioned2011-05-15T16:03:27Z
dc.date.available2011-05-15T16:03:27Z
dc.date.issued2003
dc.description.abstractThe stilbene resveratrol is a stress metabolite produced by Vitis vinifera grapevines during fungal infection, wounding or UV radiation. Resveratrol is synthesised particularly in the skins of grape berries and only trace amounts are present in the fruit flesh. Red wine contains a much higher resveratrol concentration than white wine, due to skin contact during fermentation. Apart from its antifungal characteristics, resveratrol has also been shown to have cancer chemopreventive activity and to reduce the risk of coronary heart disease. It acts as an antioxidant and anti-mutagen and has the ability to induce specific enzymes that metabolise carcinogenic substances. The objective of this pilot study was to investigate the feasibility of developing wine yeasts with the ability to produce resveratrol during fermentation in both red and white wines, thereby increasing the wholesomeness of the product. To achieve this goal, the phenylpropanoid pathway in Saccharomyces cerevisiae would have to be introduced to produce p-coumaroyl-CoA, one of the substrates required for resveratrol synthesis. The other substrate for resveratrol synthase, malonyl-CoA, is already found in yeast and is involved in de novo fatty-acid biosynthesis. We hypothesised that production of p-coumaroyl-CoA and resveratrol can be achieved by co-expressing the coenzyme-A ligase-encoding gene (4CL216) from a hybrid poplar and the grapevine resveratrol synthase gene (vst1) in laboratory strains of S. cerevisiae. This yeast has the ability to metabolise p-coumaric acid, a substance already present in grape must. This compound was therefore added to the synthetic media used for the growth of laboratory cultures. Transformants expressing both the 4CL216 and vst1 genes were obtained and tested for production of resveratrol. Following β-glucosidase treatment of organic extracts for removal of glucose moieties that are typically bound to resveratrol, the results showed that the yeast transformants had produced the resveratrol β-glucoside, piceid. This is the first report of the reconstruction of a biochemical pathway in a heterologous host to produce resveratrol. © 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.
dc.description.versionArticle
dc.identifier.citationFEMS Yeast Research
dc.identifier.citation4
dc.identifier.citation1
dc.identifier.issn15671356
dc.identifier.other10.1016/S1567-1356(03)00157-0
dc.identifier.urihttp://hdl.handle.net/10019.1/12628
dc.subject4 coumaroyl coenzyme a
dc.subjectbeta glucosidase
dc.subjectcoenzyme A
dc.subjectfatty acid
dc.subjectlong chain fatty acid coenzyme A ligase
dc.subjectmalonyl coenzyme A
dc.subjectorganic compound
dc.subjectpiceid
dc.subjectresveratrol
dc.subjectresveratrol synthase
dc.subjectsynthetase
dc.subjectunclassified drug
dc.subjectantioxidant activity
dc.subjectarticle
dc.subjectbiosynthesis
dc.subjectcontrolled study
dc.subjectculture medium
dc.subjectenzyme substrate
dc.subjectenzyme synthesis
dc.subjectfatty acid synthesis
dc.subjectfeasibility study
dc.subjectfermentation
dc.subjectfungal strain
dc.subjectgene expression
dc.subjecthybridization
dc.subjecthypothesis
dc.subjectmetabolic engineering
dc.subjectnonhuman
dc.subjectSaccharomyces cerevisiae
dc.subjectwine industry
dc.subjectAcyltransferases
dc.subjectAntioxidants
dc.subjectCoenzyme A Ligases
dc.subjectSaccharomyces cerevisiae
dc.subjectStilbenes
dc.subjectTransformation, Genetic
dc.subjectWine
dc.subjectPopulus berolinensis
dc.subjectSaccharomyces
dc.subjectSaccharomyces cerevisiae
dc.subjectVitis
dc.subjectVitis sp.
dc.subjectVitis vinifera
dc.titleMetabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol
dc.typeArticle
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