Journal
CHEMISTRY & BIOLOGY
Volume 20, Issue 2, Pages 232-240Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2012.11.011
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Funding
- Natural Science and Engineering Research Council
- Ontario Graduate Scholarship
- Canadian Institutes of Health Research (MOP) [97729]
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The ligands that interact with the vast majority of small-molecule binding transcription factors are unknown, a significant gap in our understanding of sensory perception by cells. TetR-family regulators (TFRs) are found in most prokaryotes and are involved in regulating virtually every aspect of prokaryotic life however only a few TFRs have been characterized. We report the application of phylogenomics to the identification of cognate ligands for TFRs. Using phylogenomics we identify a TFR, KijR, that responds to the antibiotic kijanimicin. We go on to show that KijR represses a gene, kijX, which confers resistance to kijanimicin. Finally we show that KijX inactivates kijanimicin by the hydrolytic removal of sugar residues. This is a demonstration of antibiotic resistance by deglycosylation.
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