Production of resveratrol from tyrosine in metabolically engineered Saccharomyces cerevisiae

• Published in: Enzyme and microbial technology 2012-09, Vol.51 (4), p.211-216
• Main Authors: Shin, So-Yeon, Jung, Sang-Min, Kim, Myoung-Dong, Han, Nam Soo, Seo, Jin-Ho
• Format: Article
• Language: English
• Subjects: 4-Coumarate:coenzyme A ligase (4CL1); ACC1 gene; Acetyl-CoA carboxylase; Acyltransferases - genetics; Acyltransferases - metabolism; Amino acids; Ammonia; Arabidopsis - enzymology; Arabidopsis - genetics; Arabidopsis thaliana; Arachis - enzymology; Arachis - genetics; Arachis hypogaea; Biotechnology - methods; Cinnamic acid; Cinnamic acid 4-hydroxylase (C4H); Coenzyme A; Coenzyme A Ligases - genetics; Coenzyme A Ligases - metabolism; Coumaric Acids - metabolism; Enzymes; Fermentation; Galactose; Genetic Engineering - methods; Genetically engineered microorganisms; Heart diseases; p-Coumaric acid; Phenylalanine; Phenylalanine ammonia lyase (PAL); Phenylalanine Ammonia-Lyase - genetics; Phenylalanine Ammonia-Lyase - metabolism; Polyphenols; Promoters; Propionates; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Resveratrol; Rhodosporidium toruloides; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Stilbene synthase (STS); Stilbenes - metabolism; Trihydroxystilbene synthase; Tyrosine; Tyrosine - metabolism; Vitaceae; Wine
• ISSN: 0141-0229; 1879-0909
• DOI: 10.1016/j.enzmictec.2012.06.005

► p-Coumaric acid of 10.5mg/L produced in recombinant yeast expressing PAL and C4H. ► Resveratrol of 3.4mg/L produced from tyrosine in yeast introducing four genes. ► Production of resveratrol improved to 4.3mg/L by increasing pool of malonyl-CoA. ► Addition of tyrosine led to increase in resveratrol produced up to 5.8mg/L. 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 2.6mg/L p-coumaric acid and 3.3mg/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 (4.3mg/L). Furthermore, when tyrosine was supplemented in the medium, the concentration of resveratrol increased up to 5.8mg/L. This result illustrates a possible strategy for developing metabolically engineered yeast strain for the economical production of resveratrol from cheap amino acids.