title: Identification and characterization of the pyridomycin biosynthetic gene cluster of Streptomyces pyridomyceticus NRRL B-2517.
abstract: Pyridomycin is a structurally unique antimycobacterial cyclodepsipeptide containing rare 3-(3-pyridyl)-l-alanine and 2-hydroxy-3-methylpent-2-enoic acid moieties. The biosynthetic gene cluster for pyridomycin has been cloned and identified from Streptomyces pyridomyceticus NRRL B-2517. Sequence analysis of a 42.5-kb DNA region revealed 26 putative open reading frames, including two nonribosomal peptide synthetase (NRPS) genes and a polyketide synthase gene. A special feature is the presence of a polyketide synthase-type ketoreductase domain embedded in an NRPS. Furthermore, we showed that PyrA functioned as an NRPS adenylation domain that activates 3-hydroxypicolinic acid and transfers it to a discrete peptidyl carrier protein, PyrU, which functions as a loading module that initiates pyridomycin biosynthesis in vivo and in vitro. PyrA could also activate other aromatic acids, generating three pyridomycin analogues in vivo.
authors: State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
authors: Tingting
authors: T
authors: Huang
authors: Yemin
authors: Y
authors: Wang
authors: Jun
authors: J
authors: Yin
authors: Yanhua
authors: Y
authors: Du
authors: Meifeng
authors: M
authors: Tao
authors: Jing
authors: J
authors: Xu
authors: Wenqing
authors: W
authors: Chen
authors: Shuangjun
authors: S
authors: Lin
authors: Zixin
authors: Z
authors: Deng
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D005810:Multigene Family; D009842:Oligopeptides / Q000096:biosynthesis*; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D009842:Oligopeptides; D010453:Peptide Synthases; C458999:pyridomycin