Artificial biosynthesis of resveratrol derivatives in a tyrosine overproducing Escherichia coli strain

Resveratrol, which is a polyphenolic antioxidant, is dose-dependent when used to provide health benefits, to enhance stress resistance, and to extend lifespans. However, even though resveratrol has therapeutic benefits, its clinical therapeutic effect is limited owing to its low oral bioavailability. An Escherichia coli system was developed that contains an artificial biosynthetic pathway that produces resveratrol and resveratrol derivatives, such as resveratrol glucoside derivatives (piceid and resveratroloside) and methylated resveratrol derivatives (pinostilbene, 3,5-dihydroxy-4’-methoxystilbene, 3,4’-dimethoxy-5-hydroxystilbene, and 3,5,4’-trimethoxystilbene), from simple carbon sources. This artificial biosynthetic pathway contains a glycosyltransferase (from Bacillus) or codon-optimized O-methyltransferase genes addition (from sorghum) with resveratrol biosynthetic genes. The produced resveratrol derivatives were verified through the presence of a product peak(s) and also through LC/MS analyses. In addition, these heterologous pathways extended in E. coli that had biosynthesis machinery overproducing tyrosine. The strategy used in this research demonstrates the first harnessing of E. coli for de novo synthesis of resveratrol derivatives from a simple sugar medium. [This work was supported in part by a grant from the KRIBB Research Initiative Program and by the GRDC Program (NRF-2010-00719)]