链霉菌沉默基因簇激活在天然产物生物合成中的研究进展  

Advances in the activation of cryptic biosynthetic gene clusters of Streptomyces in biosynthesis of natural products

作　　者：马正 施越 章金垚 俞晓平 MA Zheng;SHI Yue;ZHANG Jinyao;YU Xiaoping(Zhejang Provincial Key Laboratory of Biometrology,Inspection and Quarantine,Collegeof Life Sciences,China Jiliang University,Hangzhou 310018,China)

机构地区：[1]中国计量大学生命科学学院浙江省生物计量及检验检疫技术重点实验室,浙江杭州310018

出　　处：《中国计量大学学报》2022年第2期272-280,共9页Journal of China University of Metrology

基　　金：国家自然科学基金项目(No.31972320);浙江省自然科学基金项目(No.LZ22C140002)。

摘　　要：目的:本文概述了目前激活链霉菌沉默生物合成基因簇的研究进展,并对其应用进行了讨论和展望。方法:基因测序技术揭示链霉菌基因组中蕴含几十个次级代谢产物生物合成基因簇,而这些基因簇在常规培养条件下往往处于“沉默状态”,不表达或低表达,目前主要有沉默基因簇的异源表达、调控基因修饰、核糖体工程技术、基于报告基因指示等多种策略用于链霉菌中沉默基因簇的激活。结果:链霉菌中的沉默基因簇可被定向或非定向的“激活”,并实现众多新型天然化合物的合成。结论:链霉菌沉默基因簇的激活已成为新药开发的重要来源。Aims: In this study, advances in activation of silent secondary metabolite biosynthetic gene clusters in Streptomyces were summarized and the applications were briefly discussed and proposed in future.Methods: The development of genome-sequencing reveals that the dozens of secondary metabolite biosynthetic gene cluster are located at genome of Streptomyces. However, these secondary metabolite biosynthetic gene clusters were “silent”, namely were not expressed or slightly expressed under normal culture conditions. Several strategies such as heterologous expression of silent cluster, modification of regulatory gene, ribosome engineering, reporter gene-guided, were employed to use for activation of silent secondary metabolite biosynthetic gene clusters.Results: The silent secondary metabolite biosynthetic gene clusters of Streptomyces can be activated directly or indirectly, and further many novel natural products could be created.Conclusions: The activation of silent clusters of Streptomyces could represent a large source of development of new drugs.

关 键 词：链霉菌 沉默生物合成基因簇 异源表达 核糖体工程 报告基因 激活 

分 类 号：Q933[生物学—微生物学]