A-94964, a novel inhibitor of bacterial translocase I, produced by Streptomyces sp. SANK 60404. I. Taxonomy, isolation and biological activity

J Antibiot (Tokyo). 2008 Sep;61(9):537-44. doi: 10.1038/ja.2008.71.

Abstract

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.

MeSH terms

  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / enzymology*
  • Disaccharides / isolation & purification*
  • Disaccharides / pharmacology
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Pyrimidine Nucleotides / isolation & purification*
  • Pyrimidine Nucleotides / pharmacology
  • Streptomyces / classification*
  • Streptomyces / metabolism
  • Transferases (Other Substituted Phosphate Groups) / antagonists & inhibitors*
  • Tunicamycin / pharmacology

Substances

  • A 94964
  • Anti-Bacterial Agents
  • Disaccharides
  • Enzyme Inhibitors
  • Pyrimidine Nucleotides
  • Tunicamycin
  • Transferases (Other Substituted Phosphate Groups)
  • phospho-N-acetylmuramoyl pentapeptide transferase