RESUMO
Bacterial phospho-N-acetylmuramyl-pentapeptide translocase (translocase I: EC 2.7.8.13) is a key enzyme in peptidoglycan biosynthesis, and a known target of antibiotics. Here we report a novel nucleoside inhibitor against translocase I, A-94964, isolated from the culture broth of the strain Streptomyces sp. SANK 60404. A-94964 inhibited bacterial translocase I with IC50 value of 1.1 microg/ml, and showed antimicrobial activities against Staphylococcus aureus and Enterococcus faecalis with MIC of 100 and 50 microg/ml, respectively. A-94964 did not show cytotoxicity against mammalian cell lines.
Assuntos
Antibacterianos/isolamento & purificação , Bactérias/enzimologia , Dissacarídeos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Nucleotídeos de Pirimidina/isolamento & purificação , Streptomyces/classificação , Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores , Antibacterianos/farmacologia , Dissacarídeos/farmacologia , Inibidores Enzimáticos/farmacologia , Células HeLa , Humanos , Nucleotídeos de Pirimidina/farmacologia , Streptomyces/metabolismo , Tunicamicina/farmacologiaRESUMO
Bacterial phospho-N-acetylmuramyl-pentapeptide translocase (translocase I: EC 2.7.8.13) is a key enzyme in peptidoglycan biosynthesis, and a known target of antibiotics. Here we report a new nucleoside inhibitor for translocase I, A-102395, isolated from the culture broth of the strain Amycolatopsis sp. SANK 60206. A-102395 is a new derivative of capuramycin that has the benzene with a uniquely substituted chain instead of an aminocaprolactam. A-102395 is a potent inhibitor of bacterial translocase I with IC50 value of 11 nM, but possesses no antimicrobial activity against various strains tested.
