Characterization of AziR, a resistance protein of the DNA cross-linking agent azinomycin B

Jennifer Foulke-Abel; Gilbert T. Kelly; Huitu Zhang; Coran M.H. Watanabe

doi:10.1039/c1mb05136a

Characterization of AziR, a resistance protein of the DNA cross-linking agent azinomycin B

Jennifer Foulke-Abel, Gilbert T. Kelly, Huitu Zhang, Coran M.H. Watanabe

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7 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2563-2570
Number of pages	8
Journal	Molecular BioSystems
Volume	7
Issue number	9
DOIs	https://doi.org/10.1039/c1mb05136a
State	Published - Sep 1 2011
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Molecular Biology

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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.",

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Characterization of AziR, a resistance protein of the DNA cross-linking agent azinomycin B

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