Using Unnatural Protein Fusions to Engineer Resveratrol Biosynthesis in Yeast and Mammalian Cells

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• 作者：Yansheng Zhang ; Song-Zhe Li ; Jia Li ; Xiangqing Pan ; Rebecca E. Cahoon ; Jan G. Jaworski ; Xuemin Wang ; Joseph M. Jez ; Feng Chen ; Oliver Yu
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：October 11, 2006
• 年：2006
• 卷：128
• 期：40
• 页码：13030 - 13031
• 全文大小：70K
• 年卷期：v.128,no.40(October 11, 2006)
• ISSN：1520-5126

文摘

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.