Systematic Engineering of Saccharomyces cerevisiae for the De Novo Biosynthesis of Genistein and Glycosylation Derivatives
Journal article, 2024

Isoflavones are predominantly found in legumes and play roles in plant defense and prevention of estrogen-related diseases. Genistein is an important isoflavone backbone with various biological activities. In this paper, we describe how a cell factory that can de novo synthesize genistein was constructed in Saccharomyces cerevisiae. Different combinations of isoflavone synthase, cytochrome P450 reductase, and 2-hydroxyisoflavone dehydratase were tested, followed by pathway multicopy integration, to stably de novo synthesize genistein. The catalytic activity of isoflavone synthase was enhanced by heme supply and an increased intracellular NADPH/NADP+ ratio. Redistribution of the malonyl-CoA flow and balance of metabolic fluxes were achieved by adjusting the fatty acid synthesis pathway, yielding 23.33 mg/L genistein. Finally, isoflavone glycosyltransferases were introduced into S. cerevisiae, and the optimized strain produced 15.80 mg/L of genistin or 10.03 mg/L of genistein-8-C-glucoside. This is the first de novo synthesis of genistein-8-C-glucoside in S. cerevisiae, which is advantageous for the green industrial production of isoflavone compounds.

genistein

heme

glycosylation

isoflavones

malonyl-CoA

Author

Yongtong Wang

Hunan University

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Zhiqiang Xiao

Hunan University

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Siqi Zhang

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Hunan University

Xinjia Tan

Hunan University

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Yifei Zhao

Hunan Academy of Agricultural Sciences

Hunan University

Hunan Agricultural Product Processing Institute

Juan Liu

Hunan University

Hunan Agricultural Product Processing Institute

Hunan Academy of Agricultural Sciences

Chalmers, Life Sciences, Systems and Synthetic Biology

Ning Jiang

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Yang Shan

Hunan University

Hunan Academy of Agricultural Sciences

Hunan Agricultural Product Processing Institute

Journal of Fungi

2309608X (eISSN)

Vol. 10 3 176

Subject Categories

Biochemistry and Molecular Biology

DOI

10.3390/jof10030176

More information

Latest update

8/7/2024 9