Profiling influences of gene overexpression on heterologous resveratrol production in Saccharomyces cerevisiae

Abstract

Metabolic engineering of heterologous resveratrol production in Saccharomyces cerevisiae faces challenges as the precursor L-tyrosine is stringently regulated by a complex biosynthetic system. We overexpressed the main gene targets in the upstream pathways to investigate their influences on the downstream resveratrol production. Single-gene overexpression and DNA assembly-directed multigene overexpression affect the production of resveratrol as well as its precursor p-coumaric acid. Finally, the collaboration of selected gene targets leads to an optimal resveratrol production of 66.14±3.74 mg·L^–1, 2.27 times higher than the initial production in YPD medium (4% glucose). The newly discovered gene targets TRP1 expressing phosphoribosylanthranilate isomerase, ARO3 expressing 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase, and 4CL expressing 4-coumaryl-CoA ligase show notable positive impacts on resveratrol production in S. cerevisiae.

Key words： resveratrol; aromatic amino acid; DNA assembly; metabolic engineering; gene overexpression

Acknowledgments

The authors declare no competing financial interest. This work was funded by the National Basic Research Program of China (973 Program, Grant No. 2014CB745100) and the National High Technology Research and Development Program of China (863 Program, Grant No. 2012AA02A701), the International S&T Cooperation Program of China (2015DFA00960), and the National Natural Science Foundation of China (Major Program, Grant No. 21390203).ƒ

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11705-016-1601-3 and is accessible for authorized users.

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