title: Characterization of AziR, a resistance protein of the DNA cross-linking agent azinomycin B.
abstract: A protein identified from the Streptomyces sahachiroi genome exhibits a protective effect against the DNA alkylator azinomycin B when heterologously expressed in S. lividans and E. coli. The protein, dubbed AziR for azinomycin resistance, is homologous to aminoglycoside phosphotransferases but behaves as an azinomycin binding protein and fails to chemically modify azinomycin. While AziR confers resistance to azinomycin B, it is inactive against aminoglycoside antibiotics and other DNA alkylators. A nucleic acid staining assay indicates that the protein enhances cell survival, and also prevents DNA damage effects normally observed following azinomycin treatment. Knowledge of an azinomycin resistance mechanism aids in setting the stage for future engineered biosynthesis of functionally useful azinomycin analogues.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Foulke-Abel
authors.forename: Gilbert T
authors.initials: GT
authors.lastname: Kelly
authors.forename: Huitu
authors.initials: H
authors.lastname: Zhang
authors.forename: Coran M H
authors.initials: CM
authors.lastname: Watanabe
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013302:Streptomyces / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010455:Peptides; C051055:azinomycin B