Development of a Yeast Cell Factory for Resveratrol Production

Resveratrol is a natural polyphenol with antioxidative, cardioprotective, and antitumor activities. In the present study, we turn to produce resveratrol directly from glucose in Saccharomyces cerevisiae. Phenylalanine/tyrosine ammonia lyase activity was combined with expression of p-coumarate-CoA ligase from Arabidopsis thaliana and of resveratrol synthase from Vitis vinifera. The resulting strain produced 39.70±1.08 mg L^-1 resveratrol in mineral medium. In order to increase the supply of malonyl-CoA precursor, we have introduced acetyl-CoA synthetase from Salmonella enterica and overexpressed native aldehyde dehydrogenase and inactivation-resistant version of acetyl-CoA carboxylase. Furthermore, to produce resveratrol directly from glucose, tyrosine supply was improved by overexpression of feedback-resistant versions of chorismate mutase and 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase. Finally, we optimized the expression of genes involved in the resveratrol pathway by using multiple integrations in the genome at TY elements. The results show a potential of industrial resveratrol production from glucose by engineered S. cerevisiae.