title: Stepwise increase of resveratrol biosynthesis in yeast Saccharomyces cerevisiae by metabolic engineering.
abstract: Resveratrol is a unique, natural polyphenolic compound with diverse health benefits. In the present study, we attempted to improve resveratrol biosynthesis in yeast by different methods of metabolic engineering. We first mutated and then re-synthesized tyrosine ammonia lyase (TAL) by replacing the bacteria codons with yeast-preferred codons, which increased translation and improved p-coumaric acid and resveratrol biosynthesis drastically. We then demonstrated that low-affinity, high-capacity bacterial araE transporter could enhance resveratrol accumulation, without transporting resveratrol directly. Yeast cells carrying the araE gene produced up to 2.44-fold higher resveratrol than control cells. For commercial applications, resveratrol biosynthesis was detected in sucrose medium and fresh grape juice using our engineered yeast cells. In collaboration with the Chaumette Winery of Missouri, we were able to produce resveratrol-containing white wines, with levels comparable to the resveratrol levels found in most red wines.
authors.affiliation: Donald Danforth Plant Science Center, 975 North Warson Road, Saint Louis, MO 63132, USA.
authors.forename: Yechun
authors.initials: Y
authors.lastname: Wang
authors.forename: Coralie
authors.initials: C
authors.lastname: Halls
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Michiyo
authors.initials: M
authors.lastname: Matsuno
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Oliver
authors.initials: O
authors.lastname: Yu
mesh_terms: D000642:Ammonia-Lyases / Q000096:biosynthesis* / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001693:Biological Transport, Active / Q000235:genetics; D003373:Coumaric Acids / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D011422:Propionates; D000077185:Resveratrol; D012242:Rhodobacter sphaeroides / Q000201:enzymology / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D013267:Stilbenes / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D014920:Wine / Q000382:microbiology
chemical_list: C109577:AraE protein, bacteria; D001426:Bacterial Proteins; D003373:Coumaric Acids; D003470:Culture Media; D009004:Monosaccharide Transport Proteins; D011422:Propionates; D013267:Stilbenes; D013395:Sucrose; D000642:Ammonia-Lyases; C023208:L-tyrosine ammonia-lyase; C495469:p-coumaric acid; D000077185:Resveratrol