Discovery and biosynthesis of bosamycins from sp. 120454

• Published in: Chemical science (Cambridge) 2020-09, Vol.11 (34), p.9237-9245
• Main Authors: Xu, Zi Fei, Bo, Sheng Tao, Wang, Mei Jing, Shi, Jing, Jiao, Rui Hua, Sun, Yang, Xu, Qiang, Tan, Ren Xiang, Ge, Hui Ming
• Format: Article
• Language: English
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d0sc03469j

Nonribosomal peptides (NRPs) that are synthesized by modular megaenzymes known as nonribosomal peptide synthetases (NRPSs) are a rich source for drug discovery. By targeting an unusual NRPS architecture, we discovered an unusual biosynthetic gene cluster ( bsm ) from Streptomyces sp. 120454 and identified that it was responsible for the biosynthesis of a series of novel linear peptides, bosamycins. The bsm gene cluster contains a unique monomodular NRPS, BsmF, that contains a cytochrome P450 domain at the N-terminal. BsmF (P450 + A + T) can selectively activate tyrosine with its adenylation (A) domain, load it onto the thiolation (T) domain, and then hydroxylate tyrosine to form 5-OH tyrosine with the P450 domain. We demonstrated a NRPS assembly line for the formation of bosamycins by genetic and biochemical analysis and heterologous expression. Our work reveals a genome mining strategy targeting a unique NRPS domain for the discovery of novel NRPs. Genome mining targeting a unique NRPS domain led to the identification of a novel class of peptides named bosamycins.