Engineering Saccharomyces cerevisiae YPH499 for Overproduction of Geranylgeraniol

文献类型： 外文期刊

第一作者： Wang, Junhua

作者： Wang, Junhua;Wang, Junhua;Chen, Wei;Li, Youran;Jiang, Wei;Gu, Zhenghua;Xu, Sha;Zhang, Liang;Ding, Zhongyang;Shi, Guiyang;Li, Youran;Jiang, Wei;Gu, Zhenghua;Xu, Sha;Zhang, Liang;Ding, Zhongyang;Shi, Guiyang;Jiang, Wei;Hu, Jinyuan

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关键词： geranylgeraniol; squalene; geranylgeranyl diphosphatesynthase; mevalonate pathway; Saccharomycescerevisiae

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：6.1； 五年影响因子：6.3 ）

ISSN： 0021-8561

年卷期： 2023 年 71 卷 25 期

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收录情况： SCI

摘要： Optimization of supply and conversionefficiency of geranylgeranyldiphosphate (GGPP) is important for enhancing geranylgeraniol (GGOH)production in Saccharomyces cerevisiae. In this study, first, a strain producing 26.92 +/- 1.59 mg/gof dry cell weight squalene was constructed with overexpression ofall genes of the mevalonate (MVA) pathway, and an engineered strainproducing 597.12 mg/L GGOH at the shake flask level was obtained.Second, through additional expression of PaGGPPs-ERG20 and PaGGPPs-DPP1, and downregulating expression of ERG9, the GGOHtiter was increased to 1221.96 mg/L. Then, a NADH HMG-CoA reductasefrom Silicibacter pomeroyi (SpHMGR) was introduced to alleviate the high dependenceof the strain upon NADPH, and the GGOH production was further increasedto 1271.14 mg/L. Finally, the GGOH titer reached 6.33 g/L after optimizingthe fed-batch fermentation method in a 5 L bioreactor, with a 24.9%improvement from the previous report. This study might acceleratethe process of developing S. cerevisiae cell factories for diterpenoid and tetraterpenoid production.

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