Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and mammalian cells

Yansheng Zhang, Song Zhe Li, Jia Li, Xiangqing Pan, Rebecca E. Cahoon, Jan G. Jaworski, Xuemin Wang, Joseph M. Jez, Feng Chen, Oliver Yu

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

Resveratrol is a naturally occurring defense compound produced by a limited number of plants in response to stresses. Besides cardiovascular benefits, this health-promoting compound has been reported to extend life spans in yeasts, flies, worms, and fish. To biosynthesize resveratrol de novo, tyrosine ammonia lyase (TAL), 4-coumarate CoA-ligase (4CL), and stilbene synthase (STS) were isolated from Rhodobacter sphaeroides, Arabidopsis thaliana, and Vitis vinifera, respectively. Yeast cells expressing 4CL and STS produce resveratrol when fed with 4-coumaric acid, the substrate of 4CL. When a translational fusion protein joining 4CL and STS was used, yeast cells produced 15-fold more resveratrol than the cotransformed cells, suggesting that physical localization of 4CL and STS facilitate resveratrol production. When the resveratrol pathway was introduced into human HEK293 cells, de novo biosynthesis was detected, leading to intracellular accumulation of resveratrol. We successfully engineered an entire plant natural product pathway into a mammalian host.

Original languageEnglish
Pages (from-to)13030-13031
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number40
DOIs
StatePublished - Oct 11 2006

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    Zhang, Y., Li, S. Z., Li, J., Pan, X., Cahoon, R. E., Jaworski, J. G., Wang, X., Jez, J. M., Chen, F., & Yu, O. (2006). Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and mammalian cells. Journal of the American Chemical Society, 128(40), 13030-13031. https://doi.org/10.1021/ja0622094