m4C DNA methylation regulates biosynthesis of daptomycin in Streptomyces roseosporus L30  

作　　者：Jiao-Le Fang Wen-Li Gao Wei-Feng Xu Zhong-Yuan Lyu Lie Ma Shuai Luo Xin-Ai Chen Xu-Ming Mao Yong-Quan Li 

机构地区：[1]Institute of Pharmaceutical Biotechnology,Zhejiang University School of Medicine,Hangzhou,310058,PR China [2]Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering,310058,Hangzhou,PR China

出　　处：《Synthetic and Systems Biotechnology》2022年第4期1013-1023,共11页合成和系统生物技术（英文）

基　　金：This work was supported by National Natural Science Foundation of China(grant number 31730002,2170057);the National Key R&D Program of China(grant number 2019YFA09005400)。

摘　　要：Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.

关 键 词：N4-methylcytosine DNA methyltransferase DAPTOMYCIN Transcriptional regulator Secondary metabolism 

分 类 号：R97[医药卫生—药品]