Overproduction of alpha-Farnesene in Saccharomyces cerevisiae by Farnesene Synthase Screening and Metabolic Engineering

文献类型： 外文期刊

第一作者： Wang, Junhua

作者： Wang, Junhua;Jiang, Wei;Zhu, Linghuan;Li, Youran;Xu, Sha;Chu, Alex;Zhang, Liang;Ding, Zhongyang;Shi, Guiyang;Wang, Junhua;Jiang, Wei;Liang, Chaojuan;Zhu, Linghuan;Li, Youran;Xu, Sha;Chu, Alex;Zhang, Liang;Ding, Zhongyang;Shi, Guiyang;Wang, Junhua;Jiang, Wei;Liang, Chaojuan;Zhu, Linghuan;Li, Youran;Xu, Sha;Chu, Alex;Zhang, Liang;Ding, Zhongyang;Shi, Guiyang;Jiang, Wei;Mo, Qin

作者机构：

关键词： alpha-farnesene; farnesene synthase; HMG-CoA reductase; squalene; metabolic engineering; Saccharomyces cerevisiae

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：4.192； 五年影响因子：4.289 ）

ISSN： 0021-8561

年卷期： 2021 年 69 卷 10 期

页码：

收录情况： SCI

摘要： Maximizing the flux of farnesyl diphosphate (FPP) to farnesene biosynthesis is the main challenge of farnesene overproduction in Saccharomyces cerevisiae. In this study, we screened a-farnesene synthase from soybean (Fsso) with a higher catalytic ability. Combining the overexpression of the mevalonate (MVA) pathway with the expression of Fsso, an engineered yeast strain producing 190.5 mg/L alpha-farnesene was screened with poor growth. By decreasing the copies of 3-hydroxy-3-methylglutarylcoenzyme (HMGR) overexpressed, the titer was increased to 417.8 mg/L. Then, the coexpression of Fsso and HMGR under the control of the GAL promoter and inactivation of lipid phosphate phosphatase encoded by DPP1 promoted the titer to 1163.7 mg/L. The titer was further increased to 1477.2 mg/L at the shake flask level with better growth by the construction of a prototrophic strain. Finally, the highest alpha-farnesene production of 10.4 g/L in S. cerevisiae was obtained by fed-batch fermentation in a 5 L bioreactor.

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