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

文献类型: 外文期刊

作者: Tan, Xinjia 1 ; Xiao, Zhiqiang 1 ; Zhang, Siqi 1 ; Wang, Yongtong 1 ; Zhao, Yifei 1 ; Lu, Qiyuan 1 ; Hu, Fanglin 1 ; Zuo, Shasha 1 ; Mao, Jiwei 4 ; Liu, Juan 2 ; Shan, Yang 1 ;

作者机构: 1.Hunan Univ, Coll Biol, Longping Branch, Changsha 410125, Peoples R China

2.Hunan Acad Agr Sci, Agr Prod Proc Inst, DongTing Lab, Changsha 410125, Peoples R China

3.Hunan Agr Prod Proc Inst, Hunan Key Lab Fruits & Vegetables Storage Proc Qua, Changsha 410125, Peoples R China

4.Chalmers Univ Technol, Dept Life Sci, SE-41296 Gothenburg, Sweden

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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