title: Production of resveratrol from tyrosine in metabolically engineered Saccharomyces cerevisiae.
abstract: Resveratrol, a polyphenol compound found in grape skins, has been proposed to account for the beneficial effects of red wine against heart disease. To produce resveratrol in Saccharomyces cerevisiae, four heterologous genes were introduced: the phenylalanine ammonia lyase gene from Rhodosporidium toruloides, the cinnamic acid 4-hydroxylase and 4-coumarate:coenzyme A ligase genes both from Arabidopsis thaliana, and the stilbene synthase gene from Arachis hypogaea. When this recombinant yeast was cultivated by batch fermentation in YP medium containing 2% galactose, it produced 2.6 mg/L p-coumaric acid and 3.3 mg/L resveratrol. In order to increase the pool of malonyl-CoA, a key precursor in resveratrol biosynthesis, the acetyl-CoA carboxylase (ACC1) gene was additionally overexpressed in the yeast by replacing the native promoter of the ACC1 gene with the stronger GAL1 promoter and this resulted in enhanced production of resveratrol (4.3 mg/L). Furthermore, when tyrosine was supplemented in the medium, the concentration of resveratrol increased up to 5.8 mg/L. This result illustrates a possible strategy for developing metabolically engineered yeast strain for the economical production of resveratrol from cheap amino acids.
authors.affiliation: Department of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Shin
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Jung
authors.forename: Myoung-Dong
authors.initials: MD
authors.lastname: Kim
authors.forename: Nam Soo
authors.initials: NS
authors.lastname: Han
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Seo
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D010367:Arachis / Q000201:enzymology / Q000235:genetics; D001709:Biotechnology / Q000379:methods; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D003373:Coumaric Acids / Q000378:metabolism; D005818:Genetic Engineering / Q000379:methods*; D010650:Phenylalanine Ammonia-Lyase / Q000235:genetics / Q000378:metabolism; D011422:Propionates; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D013267:Stilbenes / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D003373:Coumaric Acids; D011422:Propionates; D011994:Recombinant Proteins; D013267:Stilbenes; D014443:Tyrosine; D000217:Acyltransferases; C022674:stilbene synthase; D010650:Phenylalanine Ammonia-Lyase; D003066:Coenzyme A Ligases; C495469:p-coumaric acid; D000077185:Resveratrol