Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, United States.
J Am Chem Soc. 2010 Nov 10;132(44):15544-6. doi: 10.1021/ja108061c.
The first mechanistic insight into 2-thiosugar production in an angucycline-type antibiotic, BE-7585A, is reported. d-Glucose 6-phosphate was identified as the substrate for the putative thiosugar biosynthetic protein, BexX, by trapping the covalently bonded enzyme-substrate intermediate. The site-specific modification at K110 residue was determined by mutagenesis studies and LC-MS/MS analysis. A key intermediate carrying a keto functionality was confirmed to exist in the enzyme-substrate complex. These results suggest that the sulfur insertion mechanism in 2-thiosugar biosynthesis shares similarities with that for thiamin biosynthesis.
首次报道了安杀环素类抗生素 BE-7585A 中 2-硫代糖产生的机制见解。通过捕获共价结合的酶-底物中间产物,鉴定出 d-葡萄糖 6-磷酸是假定的硫代糖生物合成蛋白 BexX 的底物。通过突变研究和 LC-MS/MS 分析确定了 K110 残基的位点特异性修饰。在酶-底物复合物中证实存在携带酮官能团的关键中间产物。这些结果表明,2-硫代糖生物合成中的硫插入机制与硫胺素生物合成的机制相似。