Engineering Saccharomyces cerevisiae for De Novo Biosynthesis of 3′-Hydroxygenistein

文献类型： 外文期刊

第一作者： Tan, Xinjia

作者： Tan, Xinjia;Xiao, Zhiqiang;Zhang, Siqi;Wang, Yongtong;Zhao, Yifei;Lu, Qiyuan;Hu, Fanglin;Zuo, Shasha;Shan, Yang;Tan, Xinjia;Xiao, Zhiqiang;Zhang, Siqi;Wang, Yongtong;Zhao, Yifei;Lu, Qiyuan;Hu, Fanglin;Zuo, Shasha;Liu, Juan;Shan, Yang;Tan, Xinjia;Xiao, Zhiqiang;Zhang, Siqi;Wang, Yongtong;Zhao, Yifei;Lu, Qiyuan;Hu, Fanglin;Zuo, Shasha;Liu, Juan;Shan, Yang;Mao, Jiwei

作者机构：

关键词： 3 '-hydroxygenistein; genistein; 2-hydroxyisoflavanonesynthase; Saccharomyces cerevisiae; metabolic engineering

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：6.2； 五年影响因子：6.4 ）

ISSN： 0021-8561

年卷期： 2025 年 73 卷 8 期

页码：

收录情况： SCI

摘要： The polyhydroxy isoflavone 3 '-hydroxygenistein (3 '-OHG) has a wide range of pharmaceutical and nutraceutical benefits. Therefore, it is important to develop an efficient and sustainable method for 3 '-OHG production. Here, we engineered the metabolic pathways of Saccharomyces cerevisiae to achieve de novo biosynthesis of 3 '-OHG. First, we screened 2-hydroxyisoflavanone synthase (IFS), cytochrome P450 reductase, and 2-hydroxyisoflavanone dehydratase from different sources and optimized the best combination via promoter engineering. Next, we demonstrated that amplification of the rate-limiting enzyme PlIFS from Pueraria lobata improved genistein production. Increasing the availability of the cofactor heme further increased genistein titer to 44.55 +/- 1.82 mg/L. Subsequently, screening and multicopy integration of isoflavone-3 '-hydroxylase achieved 13.23 +/- 0.27 mg/L 3 '-OHG from 100 mg/L naringenin. Finally, 1.40 +/- 0.02 mg/L 3 '-OHG could be achieved via the de novo biosynthesis pathway. The final strain generated in this study will facilitate the production of polyhydroxy isoflavones via the 3 '-OHG biosynthetic pathway.

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