These authors contributed equally to this work.
Self-Resistance to an Antitumor Antibiotic: A DNA Glycosylase Triggers the Base-Excision Repair System in Yatakemycin Biosynthesis†
Article first published online: 17 SEP 2012
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 51, Issue 42, pages 10532–10536, October 15, 2012
How to Cite
Xu, H., Huang, W., He, Q.-L., Zhao, Z.-X., Zhang, F., Wang, R., Kang, J. and Tang, G.-L. (2012), Self-Resistance to an Antitumor Antibiotic: A DNA Glycosylase Triggers the Base-Excision Repair System in Yatakemycin Biosynthesis . Angew. Chem. Int. Ed., 51: 10532–10536. doi: 10.1002/anie.201204109
We thank Prof. Yasuhiro Igarashi (Toyama Prefectural University,Japan) for providing the strain Streptomyces sp. TP-A0356 and yatakemycin; Prof. Magnar Bjoras (University of Oslo, Norway), for providing plasmids pT7SCII-AlkC and pT7SCII-AlkD that encode the alkC and alkD genes; and the lab of Prof. Zixin Deng of Shanghai JiaoTong University for support in obtaining MS data. This work was financially supported by grants from the National Basic Research Program of China (973 Program) 2009CB118901 and 2010CB833200, and the National Natural Science Foundation of China (90913005, 20832009, and 20921091).
- Issue published online: 10 OCT 2012
- Article first published online: 17 SEP 2012
- Manuscript Received: 27 MAY 2012
- National Basic Research Program of China. Grant Numbers: 2009CB118901, 2010CB833200
- National Natural Science Foundation of China. Grant Numbers: 90913005, 20832009, 20921091
- base excision repair;
- DNA damage;
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).