Reconstitution of biosynthetic pathway for mushroom-derived cyathane diterpenes in yeast and generation of new“non-natural”analogues

作     者：Ke Ma Yuting Zhang Cui Guo Yanlong Yang Junjie Han Bo Yu Wenbing Yin Hongwei Liu Ke Ma;Yuting Zhang;Cui Guo;Yanlong Yang;Junjie Han;Bo Yu;Wenbing Yin;Hongwei Liu

作者机构：State Key Laboratory of MycologyInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China Savaid Medical SchoolUniversity of Chinese Academy of SciencesBeijing 100049China CAS Key Laboratory of Microbial Physiological and Metabolic EngineeringInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第9期

页      面：2945-2956页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the grants from the National Key R&D program of China(Grant 2018YFD0400203 and 2017YEE0108200) the National Natural Science Foundation of China(Grant 21472233) the“Innovative Cross Team”project,CAS(Grant E0222L01R1,China) 

主　　题：Cyathane-type diterpene Biosynthesis Heterologous expression Non-enzymatic reaction 

摘      要：Mushroom-derived cyathane-type diterpenes possess unusual chemical skeleton and diverse *** efficiently supply bioactive cyathanes for deep studies and explore their structural diversity,de novo synthesis of cyathane diterpenes in a geranylgeranyl pyrophosphate engineered Saccharomyces cerevisiae is *** by homologous analyses,one new unclustered FAD-dependent oxidase EriM accounting for the formation of allyl aldehyde and three new NADP(H)-dependent reductases in the biosynthesis of cyathanes are identified and *** combinatorial biosynthetic strategy,*** strains generating twenty-two cyathane-type diterpenes,including sevenunnaturalcyathane xylosides(12,13,14a,14b,19,20,and 22)are *** 12-14,19,and 20 show significant neurotrophic effects on PC 12 cells in the dose of 6.3-25.0μmol/*** studies provide new insights into the divergent biosynthesis of mushroom-originated cyathanes and a straightforward approach to produce bioactive cyathane-type diterpenes.