The construction and optimization of engineered yeast chassis for efficient biosynthesis of 8-hydroxygeraniol

作     者：Yu Zhang Mengdi Yuan Xinxin Wu Qiuhui Zhang Yuzhu Wang Liming Zheng Tsan-Yu Chiu Huiming Zhang Lei Lan Feng Wang Ying Liao Xuemei Gong Shirui Yan Yun Wang Yue Shen Xian Fu Yu Zhang;Mengdi Yuan;Xinxin Wu;Qiuhui Zhang;Yuzhu Wang;Liming Zheng;Tsan-Yu Chiu;Huiming Zhang;Lei Lan;Feng Wang;Ying Liao;Xuemei Gong;Shirui Yan;Yun Wang;Yue Shen;Xian Fu

作者机构：BGI ResearchShenzhenChina BGI ResearchHangzhouChina Guangdong Provincial Key Laboratory of Genome Read and WriteBGI ResearchShenzhenChina BGI ResearchChangzhouChina 

出 版 物：《mLife》 (微生物（英文）)

年 卷 期：2023年第2卷第4期

页      面：438-449页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071005[理学-微生物学] 10[医学] 

基　　金：supported by grants from the National Key Research and Development Program of China (No.2021YFC2100800 to Y.Z.) the Science,Technology and Innovation Commission of Shenzhen Municipality under grant (No.JCYJ20180507183534578) the Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program (2019TQ05Y876 to Y.S.) 

主　　题：8-hydroxygeraniol biosynthesis G8H SCRaMbLE synthetic yeast 

摘      要：Microbial production of monoterpenoid indole alkaloids(MIAs)provides a sustainable and eco-friendly means to obtain compounds with high pharmaceutical ***,efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8-hydroxygeraniol catalyzed by geraniol 8-hydroxylase(G8H).In this study,we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.0 synthetic yeast and confirmed the causal role of relevant genomic *** genome mining,we identified several G8H enzymes that perform much better than the commonly used CrG8H for 8-hydroxygeraniol production in *** further showed that the N-terminus of these G8H enzymes plays an important role in cellular activity by swapping ***,the combination of the engineered chassis,optimized biosynthesis pathway,and utilization of G8H led to the final strain with more than 30-fold improvement in producing 8-hydroxygeraniol compared with the starting ***,this study will provide insights into the construction and optimization of yeast cells for efficient biosynthesis of 8-hydroxygeraniol and its derivatives.