title: Staphylococcus aureus Penicillin-Binding Protein 2 Can Use Depsi-Lipid II Derived from Vancomycin-Resistant Strains for Cell Wall Synthesis.
abstract: 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.
authors.affiliation: Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, 980-8577 (Japan), Fax: (+81) 0-22-217-6204.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yamashiro
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miya
authors.forename: Kenzo
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Maki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Arimoto
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002473:Cell Wall / Q000737:chemistry* / Q000378:metabolism; D047630:Depsipeptides / Q000737:chemistry* / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000737:chemistry* / Q000187:drug effects*; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology*; D046915:Penicillin-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry*; D010457:Peptidoglycan / Q000096:biosynthesis* / Q000737:chemistry; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D009844:Oligosaccharides; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D014640:Vancomycin; D002267:Muramoylpentapeptide Carboxypeptidase; C419802:moenomycin
keywords: antibiotics; enzymes; lipids; peptides; vancomycin