Production of resveratrol from tyrosine in metabolically engineered Saccharomyces cerevisiae

► 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 resveratro...

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Bibliographic Details
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
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Summary:► 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.
ISSN:0141-0229
1879-0909
DOI:10.1016/j.enzmictec.2012.06.005