链霉菌沉默生物合成基因簇激活策略的研究进展  

Advances in strategies for activating silent biosynthetic gene clusters in Streptomyces

作　　者：戴岩 吴旭日 陈依军 DAI Yan;WU Xuri;CHEN Yijun(Laboratory of Chemical Biology,School of Life Science and Technology,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学生命科学与技术学院化学生物学研究室

出　　处：《中国药科大学学报》2019年第4期379-388,共10页Journal of China Pharmaceutical University

基　　金：江苏省“六大人才高峰”项目资助(No.SWYY-097);江苏高校“青蓝工程”资助项目~~

摘　　要：微生物次级代谢产物因其显著的生物活性一直是新药发现与开发的重要来源之一,激增的基因组信息表明,链霉菌中存在着巨大的生物合成潜力。但目前从链霉菌中挖掘的具有新骨架或新结构单元的活性次级代谢产物数量远低于生物合成基因簇的数量,原因主要在于很多生物合成基因簇在常规实验条件下表达微弱或转录沉默。从预测生物合成基因簇的生物信息学工具入手,本文重点阐述了在天然宿主和异源宿主中激活链霉菌沉默生物合成基因簇的经典方法和最新策略,包括转录因子诱捕、报告子导向的高通量筛选以及多重CRISPR-TAR等,为挖掘链霉菌新型次级代谢产物提供了方法学参考。Microbial secondary metabolites have always been one of the important sources of discovery and development of new drugs due to their remarkable biological activities.The explosion of genome sequences has revealed that Streptomyces harbor an immensely untapped biosynthetic potential.However,the number of active secondary metabolites with new skeletons or structural units found from Streptomyces is much lower than that of biosynthetic gene clusters(BGCs),mainly due to the fact that many BGCs are either expressed weakly or transcriptionally silent under conventional laboratory conditions.Beginning with the bioinformatics tools for BGCs prediction,this review focuses on the classical approaches to activate silent BGCs of Streptomyces in native and heterologous hosts.Moreover,several new strategies including transcriptional factors decoy,reporter-guided high-throughput selection and muliplexed CRISPR-TAR were detailed,which provide methodological references for mining new secondary metabolites from Streptomyces.

关 键 词：链霉菌 次级代谢产物 沉默生物合成基因簇 生物信息学工具 基因簇激活策略 

分 类 号：R978[医药卫生—药品]