1. m4C DNA methylation regulates biosynthesis of daptomycin in Streptomyces roseosporus L30
- Author
-
Jiao-Le Fang, Wen-Li Gao, Wei-Feng Xu, Zhong-Yuan Lyu, Lie Ma, Shuai Luo, Xin-Ai Chen, Xu-Ming Mao, and Yong-Quan Li
- Subjects
N4-methylcytosine ,DNA methyltransferase ,Daptomycin ,Transcriptional regulator ,Secondary metabolism ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 - Abstract
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 in ΔsroLm3 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.
- Published
- 2022
- Full Text
- View/download PDF