Discovery and biosynthesis of bosamycins from Streptomyces sp. 120454 |
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| Authors: | Zi Fei Xu Sheng Tao Bo Mei Jing Wang Jing Shi Rui Hua Jiao Yang Sun Qiang Xu Ren Xiang Tan Hui Ming Ge |
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| Institution: | State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, School of Life Sciences, Nanjing University, 210023 P. R. China.; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023 P. R. China ; Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023 P. R. China |
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| Abstract: | 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. |
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