Fang Jiao-Le, Gao Wen-Li, Xu Wei-Feng, Lyu Zhong-Yuan, Ma Lie, Luo Shuai, Chen Xin-Ai, Mao Xu-Ming, Li Yong-Quan
Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310058, PR China.
Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering, 310058, Hangzhou, PR China.
Synth Syst Biotechnol. 2022 Jun 17;7(4):1013-1023. doi: 10.1016/j.synbio.2022.06.001. eCollection 2022 Dec.
Despite numerous studies on transcriptional level regulation by single genes in drug producing , the global regulation based on epigenetic modification is not well explored. N4-methylcytosine (m4C), an abundant epigenetic marker in ' genome, but its regulatory mechanism remains unclear. In this study, we identify a m4C methyltransferase (SroLm3) in L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism. Notably, three BGCs in Δ strain exhibited decreased expression compared to wild type. In-frame deletion of in 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
尽管在药物生产中对单个基因的转录水平调控进行了大量研究，但基于表观遗传修饰的全局调控尚未得到充分探索。N4-甲基胞嘧啶（m4C）是基因组中一种丰富的表观遗传标记，但其调控机制仍不清楚。在本研究中，我们在L30中鉴定出一种m4C甲基转移酶（SroLm3），并进行了多组学研究，揭示SroLm3是次级代谢的全局调节因子。值得注意的是，与野生型相比，Δ菌株中的三个生物合成基因簇（BGCs）表达降低。在L30中对其进行框内缺失进一步揭示了其在增强达托霉素生产中的作用。总之，我们鉴定了一种m4C甲基转移酶，揭示了m4C在次级代谢调控和红色素生物合成中的功能，并确定了一系列由m4C甲基化主导的达托霉素生物合成的新型调节因子。我们的研究进一步表明，m4C DNA甲基化可能有助于在……中从初级代谢向次级代谢的代谢转换
