Nakamura Jun, Yamashiro Hidenori, Miya Hiroto, Nishiguchi Kenzo, Maki Hideki, Arimoto Hirokazu
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, 980-8577 (Japan), Fax: (+81) 0-22-217-6204.
Chemistry. 2013 Sep 2;19(36):12104-12. doi: 10.1002/chem.201301074. Epub 2013 Jul 19.
Vancomycin-resistant Staphylococcus aureus (S. aureus) (VRSA) uses depsipeptide-containing modified cell-wall precursors for the biosynthesis of peptidoglycan. Transglycosylase is responsible for the polymerization of the peptidoglycan, and the penicillin-binding protein 2 (PBP2) plays a major role in the polymerization among several transglycosylases of wild-type S. aureus. However, it is unclear whether VRSA processes the depsipeptide-containing peptidoglycan precursor by using PBP2. Here, we describe the total synthesis of depsi-lipid I, a cell-wall precursor of VRSA. By using this chemistry, we prepared a depsi-lipid II analogue as substrate for a cell-free transglycosylation system. The reconstituted system revealed that the PBP2 of S. aureus is able to process a depsi-lipid II intermediate as efficiently as its normal substrate. Moreover, the system was successfully used to demonstrate the difference in the mode of action of the two antibiotics moenomycin and vancomycin.
耐万古霉素金黄色葡萄球菌（VRSA）利用含缩肽的修饰细胞壁前体进行肽聚糖的生物合成。转糖基酶负责肽聚糖的聚合，而青霉素结合蛋白2（PBP2）在野生型金黄色葡萄球菌的几种转糖基酶中，在聚合过程中起主要作用。然而，目前尚不清楚VRSA是否通过使用PBP2来处理含缩肽的肽聚糖前体。在此，我们描述了VRSA的细胞壁前体缩肽脂质I的全合成。利用这种化学方法，我们制备了一种缩肽脂质II类似物作为无细胞转糖基化系统的底物。重组系统表明，金黄色葡萄球菌的PBP2能够像处理其正常底物一样有效地处理缩肽脂质II中间体。此外，该系统成功地用于证明两种抗生素莫能菌素和万古霉素作用方式的差异。
