文献类型：期刊文献

英文题名：Metabolic Engineering of Yarrowia lipolytica for Enhanced De Novo Biosynthesis of Icaritin

作者：Sun, Wen-Zhuo[1];Wang, Xin[1];Fu, Meng-Yu[1];Liu, Le-Fan[1];Zhang, Ping[1];Yin, Bin-Cheng[1];Liu, Wei-Bing[1];Ye, Bang-Ce[1]

机构：[1]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2025

卷号：14

期号：4

起止页码：1142

外文期刊名：ACS SYNTHETIC BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001448294100001)】；

基金：This work was supported by National Key Research and Development Program of China (2021YFC2101500), and 2024 Double World-class Project.

语种：英文

外文关键词：Yarrowia lipolytica; icaritin; kaempferol; 8-prenylkaempferol; metabolic engineering; biosynthesis

摘要：Icaritin (ICT) is a naturally occurring flavonoid compound with notable anticancer properties, recently recognized for its efficacy in treating advanced hepatic carcinoma. Traditional methods of ICT production, including plant extraction and chemical synthesis, face challenges such as low yield and environmental concerns. This study leverages synthetic biology to construct a microbial cell factory using Yarrowia lipolytica for de novo ICT synthesis. We engineered the yeast by integrating the ICT synthesis pathway involving EsPT from Epimedium sagittatum and OsOMTm from Oryza sativa. By optimizing the metabolic pathways, including enhancing the supply of DMAPP via mevalonate pathway modifications, and fine-tuning the expression and catalytic efficiency of EsPT through truncation strategies, we significantly improved ICT yield to 247.02 mg/L-the highest microbial ICT titer reported to date. These findings lay a solid foundation for the large-scale industrial production of ICT and offer valuable insights into the biosynthesis of other flavonoid plant natural products.