Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica  

作　　者：Man Xu Wenliang Xie Zhen Luo Chun-Xiu Li Qiang Hua Jian-He Xu 

机构地区：[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

出　　处：《Synthetic and Systems Biotechnology》2023年第2期331-338,共8页合成和系统生物技术（英文）

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).

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.

关 键 词：Taxadiene Yarrowia lipolytica “Push–pull”ostrategy Multi-copy integration Fed-batch fermentation 

分 类 号：Q81[生物学—生物工程]