文献类型：期刊文献

英文题名：Programmable Biosynthesis of Plant-Derived 4′-Deoxyflavone Glycosides by an Unconventional Yeast Consortium

作者：Kang, Yijia[1];Qian, Zhilan[1];Yu, Haishuang[1];Lu, Jian[1];Zhao, Qing[2];Qiao, Xue[3];Ye, Min[3];Zhou, Xiangshan[4];Cai, Menghao[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Chenshan Bot Garden, Shanghai Key Lab Plant Funct Genom & Resources, Shanghai 201602, Peoples R China;[3]Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China;[4]China Resources Biopharmaceut Co Ltd, Shenzhen 518132, Peoples R China

年份：2024

卷号：8

期号：8

外文期刊名：SMALL METHODS

收录：;EI(收录号：20240715549952);WOS:【SCI-EXPANDED(收录号:WOS:001161597100001)】；

基金：This work was supported by the National Key Research and Development Program of China (2023YFA0914100, 2020YFA0907804, 2018YFC1706202), the 111 project (B18022) and Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, Grant 2021 Sci & Tech 03-28). The authors thank Prof. Renxiang Tan in Nanjing University, Prof. Yuanxing Zhang and Prof. Lixin Zhang's group in East China University of Science and Technology for their support of this work.

语种：英文

外文关键词：4 '-deoxyflavone glycosides; baicalin; co-culture; Pichia pastoris; plant natural products

摘要：Previous data established 4 '-deoxyflavone glycosides (4 '-DFGs) as important pharmaceutical components in the roots of rare medical plants like Scutellaria baicalensis Georgi. Extracting these compounds from plants involves land occupation and is environmentally unfriendly. Therefore, a modular ("plug-and-play") yeast-consortium platform is developed to synthesize diverse 4 '-DFGs de novo. By codon-optimizing glycosyltransferase genes from different organisms for Pichia pastoris, six site-specific glycosylation chassis are generated to be capable of biosynthesizing 18 different 4 '-DFGs. Cellular factories showed increased 4 '-DFG production (up to 18.6-fold) due to strengthened synthesis of UDP-sugar precursors and blocked hydrolysis of endogenous glycosides. Co-culturing upstream flavone-synthesis-module cells with downstream glycoside-transformation-module cells alleviated the toxicity of 4 '-deoxyflavones and enabled high-level de novo synthesis of 4 '-DFGs. Baicalin is produced at the highest level (1290.0 mg L-1) in a bioreactor by controlling the consortium through carbon-source shifting. These results provide a valuable reference for biosynthesizing plant-derived 4 '-DFGs and other glycosides with potential therapeutic applications.