Brown Daniel W, Schaab Matthew R, Birmingham William R, Armstrong Richard N
Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232-0146, USA.
Biochemistry. 2009 Mar 10;48(9):1847-9. doi: 10.1021/bi900078q.
The fosfomycin (1) resistance proteins FosA and FosX in pathogenic microorganisms are related to a catalytically promiscuous progenitor encoded in a phn operon in Mesorhizobium loti. The mlr3345 gene product (FosX(Ml)) from M. loti has a very low epoxide hydrolase activity and even lower glutathione transferase activity toward 1 and does not confer resistance to the antibiotic. In vitro homologous recombination of the mlr3345 and pa1129 genes (a fosA gene from Pseudomonas aeruginosa that does confer robust resistance to 1) produces recombinant proteins that confer resistance to 1 and indicate that the FosA resistance proteins are functionally and genetically related to mlr3345.
致病微生物中的磷霉素(1)抗性蛋白FosA和FosX与中慢生根瘤菌(Mesorhizobium loti)phn操纵子中编码的一种具有催化多效性的祖先蛋白有关。中慢生根瘤菌的mlr3345基因产物(FosX(Ml))对1具有非常低的环氧化物水解酶活性,对谷胱甘肽转移酶活性甚至更低,并且不赋予对抗生素的抗性。mlr3345和pa1129基因(来自铜绿假单胞菌的一个确实赋予对1强大抗性的fosA基因)的体外同源重组产生了赋予对1抗性的重组蛋白,并表明FosA抗性蛋白在功能和遗传上与mlr3345相关。