Cuthbertson Leslie, Ahn Sang Kyun, Nodwell Justin R
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Chem Biol. 2013 Feb 21;20(2):232-40. doi: 10.1016/j.chembiol.2012.11.011.
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.
与绝大多数小分子结合转录因子相互作用的配体尚不清楚，这是我们对细胞感官感知理解中的一个重大空白。TetR家族调节因子（TFRs）存在于大多数原核生物中，几乎参与原核生物生命的各个方面，但只有少数TFRs得到了表征。我们报告了系统发育基因组学在鉴定TFRs同源配体中的应用。利用系统发育基因组学，我们鉴定出一种对抗生素基杰那霉素有反应的TFR，即KijR。我们进一步表明，KijR抑制一个赋予对基杰那霉素抗性的基因kijX。最后，我们表明KijX通过水解去除糖残基使基杰那霉素失活。这是通过去糖基化实现抗生素抗性的一个例证。
