文献类型：期刊文献

中文题名：Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica

作者：Man Xu[1];Wenliang Xie[1];Zhen Luo[1];Chun-Xiu Li[1];Qiang Hua[1];Jian-He Xu[1]

机构：[1]State Key Laboratory of Bioreactor Engineering,Shanghai Collaborative Innovation Center for Biomanufacturing and School of Biotechnology,East China University of Science and Technology,130 Meilong Road,Shanghai,200237,China

年份：2023

卷号：8

期号：2

起止页码：331

中文期刊名：Synthetic and Systems Biotechnology

外文期刊名：合成和系统生物技术（英文）

收录：Scopus;CSCD:【CSCD2023_2024】；PubMed;

基金：supported by the National Key Research and Development Program of China(2019YFA0905000);the National Natural Science Foundation of China(21871085 and 31971380);the Fundamental Research Funds for the Central Universities(222201714026).

语种：英文

中文关键词：Taxadiene;Yarrowia lipolytica;“Push–pull”ostrategy;Multi-copy integration;Fed-batch fermentation

摘要：Taxadiene is an important precursor for the biosynthesis of highly effective anticancer drug paclitaxel,but its microbial biosynthesis yield is very low.In this study,we employed Yarrowia lipolytica as a microbial host to produce taxadiene.First,a“push–pull”strategy was adopted to increase taxadiene production by 234%.Then taxadiene synthase was fused with five solubilizing tags respectively,leading a maximum increase of 62.3%in taxadiene production when fused with SUMO.Subsequently,a multi-copy iterative integration method was used to further increase taxadiene titer,achieving the maximum titer of 23.7 mg/L in shake flask culture after three rounds of integration.Finally,the taxadiene titer was increased to 101.4 mg/L by optimization of the fed-batch fermentation conditions.This is the first report of taxadiene biosynthesis accomplished in Y.lipolytica,serving as a good example for the sustainable production of taxadiene and other terpenoids in this oleaginous yeast.