AdpA lin regulates lincomycin and melanin biosynthesis by modulating precursors flux in Streptomyces lincolnensis

作者：Yajing Kang, Wei Wu, Feixue Zhang, Lei Chen, Ruida Wang, Ye Jiang, Haizhen Wu, Huizhan Zhang · 发表于：Journal of Basic Microbiology · 年份：2023 · DOI：10.1002/jobm.202200692 · 被引用次数：14 · 研究领域：Microbial Natural Products and Biosynthesis、RNA and protein synthesis mechanisms、Genomics and Phylogenetic Studies

Abstract Lincomycin is one of the most important antibiotics. However, transcriptional regulation network of secondary metabolism in Streptomyces lincolnensis , the lincomycin producer, remained obscure. AdpA from S. lincolnensis (namely AdpA lin ) has been proved to activate lincomycin biosynthesis. Here we found that both lincomycin and melanin took l ‐tyrosine as precursor, and AdpA lin activated melanin biosynthesis as well. Three tyrosinases, MelC2, MelD2, and MelE, and one tyrosine peroxygenase, LmbB2, participated in lincomycin and melanin biosynthesis in different ways. For melanin biosynthesis, MelC2 was the only key enzyme required. For lincomycin biosynthesis, MelD2 and LmbB2 were positive factors and were suggested to convert l ‐tyrosine to l‐dihydroxyphenylalanine ( l ‐DOPA). Otherwise, MelC2 and MelE were negative factors for lincomycin biosynthesis and they were supposed to oxidize l ‐DOPA to generate melanin and certain unknown metabolite, respectively. Based on in silico analysis combined with electrophoretic mobility shift assays (EMSAs), we proved that AdpA lin directly interacted with promoters of melC, melD , and melE by binding to putative AdpA‐binding sites in vitro. Moreover, in vivo experiments revealed that AdpA lin positively regulated the transcription of melC and melE , but negatively regulated melD . In conclusion, AdpA lin was the switch of secondary metabolism in S. lincolnensis , and it modulated precursor flux of lincomycin and melanin biosyn...