Self-Resistance to an Antitumor Antibiotic: A DNA Glycosylase Triggers the Base-Excision Repair System in Yatakemycin Biosynthesis

Resistance is (not) futile: The yatakemycin biosynthetic gene cluster involves the ytkR2 gene, which encodes a protein with homology to a recently discovered bacterial DNA glycosylase. Genetic validation in vivo, biochemical assays, and in vitro mutagenesis studies revealed that YtkR2 confers resist...

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Veröffentlicht in:	Angewandte Chemie International Edition 2012-10, Vol.51 (42), p.10532-10536
Hauptverfasser:	Xu, Hui, Huang, Wei, He, Qing-Li, Zhao, Zhi-Xiong, Zhang, Feng, Wang, Renxiao, Kang, Jingwu, Tang, Gong-Li
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Sequence Antibiotics Antibiotics, Antineoplastic - pharmacology Bacillus cereus - genetics Bacillus cereus - metabolism Bacteria base excision repair Base Sequence Biochemistry Cloning, Molecular Clusters Deoxyribonucleic acid DNA Damage DNA Glycosylases - genetics DNA Glycosylases - metabolism DNA Repair Drug Resistance, Neoplasm Genes Genetics Indoles - analysis Indoles - metabolism Models, Molecular Molecular Sequence Data Pyrroles - analysis Pyrroles - metabolism Recognition Streptomyces - genetics Streptomyces - metabolism yatakemycin YtkR2
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Zusammenfassung:	Resistance is (not) futile: The yatakemycin biosynthetic gene cluster involves the ytkR2 gene, which encodes a protein with homology to a recently discovered bacterial DNA glycosylase. Genetic validation in vivo, biochemical assays, and in vitro mutagenesis studies revealed that YtkR2 confers resistance for the bacteria by specifically recognizing and cleaving the YTM‐modified base (see scheme).
ISSN:	1433-7851 1521-3773
DOI:	10.1002/anie.201204109