An intricate regulation of Wbl A controlling production of silent tylosin analogues and abolishment of expressible nikkomycin  

作　　者：Yue Li Hanye Guan Jingjing Li Jihui Zhang Yanyan Wang Jine Li Huarong Tan 

机构地区：[1]State Key Laboratory of Microbial Resources,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Science China(Life Sciences)》2023年第3期612-625,共14页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Program of China(2020YFA0907800);the National Natural Science Foundation of China(32170043,82173720);the Beijing Natural Science Foundation(7212153)。

摘　　要：Genome sequencing has revealed that actinomycetes possess the potential to produce many more secondary metabolites than previously thought.The existing challenge is to devise efficient methods to activate these silent biosynthetic gene clusters(BGCs).In Streptomyces ansochromogenes,disruption of wbl A,a pleiotropic regulatory gene,activated the expression of cryptic tylosin analogues and abolished nikkomycin production simultaneously.Overexpressing pathway-specific regulatory genes tylR1 and tylR2 can also trigger the biosynthesis of silent tylosin analogues,in which TylR1 exerted its function via enhancing tylR2 expression.Bacterial one-hybrid system experiments unveiled that Wbl A directly inhibits the transcription of tylR1 and tylR2 to result in the silence of tylosin analogues BGC.Furthermore,Wbl A can activate the nikkomycin production through up-regulating the transcription of pleiotropic regulatory gene adp A.More interestingly,Adp A can activate san G(an activator gene in nikkomycin BGC)but repress wbl A.Our studies provide a valuable insight into the complex functions of pleiotropic regulators.

关 键 词：Streptomyces ansochromogenes silent gene cluster wblA tylosin analogues pleiotropic regulatory gene secondary metabolite biosynthesis 

分 类 号：Q78[生物学—分子生物学]