Discovery and biosynthesis of bosamycins from Streptomyces sp. 120454
| Autor: | Jing Shi, Sheng Tao Bo, Rui Hua Jiao, Qiang Xu, Ren-Xiang Tan, Hui Ming Ge, Mei Jing Wang, Yang Sun, Zi Fei Xu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification biology 010405 organic chemistry Drug discovery General Chemistry Computational biology biology.organism_classification 01 natural sciences Streptomyces 0104 chemical sciences 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Biosynthesis chemistry Nonribosomal peptide Gene cluster Heterologous expression Tyrosine Adenylylation |
| Zdroj: | Chemical Science. 11:9237-9245 |
| ISSN: | 2041-6539 2041-6520 |
| DOI: | 10.1039/d0sc03469j |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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