文献类型：期刊文献

英文题名：Biosynthesis of plant vitexin-derived flavonoid glycosides in yeast

作者：Qian, Zhilan[1];Yu, Haishuang[1];Song, Chenglin[2];Zhang, Yang[2];Liu, Qi[1];Qu, Xudong[3,4,5];Ye, Min[2,6];Qiao, Xue[2,6];Cai, Menghao[1,7]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China;[3]Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai, Peoples R China;[4]Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai, Peoples R China;[5]Shanghai Jiao Tong Univ, Zhangjiang Inst Adv Study, Shanghai, Peoples R China;[6]Peking Univ, Yunnan Baiyao Int Med Res Ctr, Beijing, Peoples R China;[7]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, Shanghai, Peoples R China

年份：2026

卷号：5

期号：3

外文期刊名：NATURE SYNTHESIS

收录：WOS:【ESCI(收录号:WOS:001632066000001)】；

基金：This work was supported by the National Key Research and Development Program of China (2023YFA0914100/02), the Shanghai Explorer Program (24TS1411600), the National Natural Science Foundation of China (32201206 and 82425059) and the 111 project (B18022). We thank Y. Zhang and Y. Fu of Sichuan University for their gift of the pDEST17-SIPPO F plasmid.

语种：英文

摘要：Post-modified flavonoids from plants exhibit diverse chemical structures and bioactivities, making them valuable in pharmaceuticals and health-promoting foods. Synthetic biology has facilitated the microbial synthesis of post-modified flavonoids as an alternative to traditional plant extraction. Nevertheless, de novo biosynthesis achieves only limited production levels (milligrams per litre). In this study, we aimed to develop yeast for the bioproduction of plant-derived medicinal flavonoid monoglycosides (vitexin and orientin) and diglycosides (2 ''-O-galactosylvitexin and 2 ''-O-galactosylorientin) in high yields. We elucidated the complete biosynthetic pathways in Komagataella phaffii, an industrial yeast. Systematic metabolic engineering of the building blocks (tyrosine, malonyl-coenzyme A and sugar donors) along with parallel pathways enhanced product titres to around 10 g l(-1). Comparative omics analysis of the variations in flavonoid glycosides production on ethanol versus glucose revealed new targets to improve the synthesis. The integration of strategies for the generation of ATP, cofactor balancing and hydrolase inactivation boosted product titres to >26 g l(-1). The described strains and procedures represent an important advance in the production of flavonoid glycosides from simple carbon sources.