title: Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis.
abstract: Azinomycin B is a complex natural product containing densely assembled functionalities with potent antitumor activity. Cloning and sequence analysis of the azi gene cluster revealed an iterative type I polyketide synthase (PKS) gene, five nonribosomal peptide synthetases (NRPSs) genes and numerous genes encoding the biosynthesis of unusual building blocks and tailoring steps for azinomycin B production. Characterization of AziB as a 5-methyl-naphthoic acid (NPA) synthase showed a distinct selective reduction pattern in aromatic polyketide biosynthesis governed by bacterial iterative type I PKSs. Heterologous expression established the PKS-post modification route from 5-methyl-NPA to reach the first building block 3-methoxy-5-methyl-NPA. This proposed azinomycin B biosynthetic pathway sets the stage to investigate the enzymatic mechanisms for building structurally unique and pharmaceutically important groups, including the unprecedented azabicyclic ring system and highly active epoxide moiety.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
authors.forename: Qunfei
authors.initials: Q
authors.lastname: Zhao
authors.forename: Qingli
authors.initials: Q
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Mancheng
authors.initials: M
authors.lastname: Tang
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Kang
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.forename: Gongli
authors.initials: G
authors.lastname: Tang
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015723:Gene Library; D005798:Genes, Bacterial; D016678:Genome; D036341:Intercellular Signaling Peptides and Proteins; D008956:Models, Chemical; D008957:Models, Genetic; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000737:chemistry; D005810:Multigene Family; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; D036341:Intercellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D009281:Naphthalenes; D010455:Peptides; C051055:azinomycin B; C085312:1-naphthoic acid; D048630:Polyketide Synthases