A-94964, a Novel Inhibitor of Bacterial Translocase I, Produced by Streptomyces sp. SANK 60404

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 IC 50 value of 1.1 m g/ml, and showed antimicrobial activities against Staphylococcus aureus and Enterococcus faecalis with MIC of 100 and 50 m g/ml, respectively. A-94964 did not show cytotoxicity against mammalian cell lines.

A novel assay of bacterial peptidoglycan synthesis for natural product screening

“…We applied this method to high-throughput screening of natural products and discovered novel translocase I inhibitors. [13][14][15][16][17][32][33][34][35] As the assay is sensitive and robust enough, we tried to measure MurF activity by coupling with this reaction (Figure 1). For that purpose, we first established a large-scale fermentation protocol for UDPMurNAc-tripeptide to prepare the labeled substrate UDP-MurNAcdansyltripeptide.…”

A-94964, Novel Inhibitor of Bacterial Translocase I, Produced by Streptomyces sp. SANK 60404

“…1 H-31 P long-range couplings were observed from each of the H-7Ј and H-1ٞ protons. Furthermore, a two-bond 13 C-31 P coupling was also observed with the anomeric carbon of the amino sugar (C-1ٞ) with a J value of 6.1 Hz in the 13 C-NMR spectrum. By these observations, it was proved that partial structures A and B were connected through the phosphate group.…”

“…SANK 60404. In our preceding paper [13], we described the taxonomy of the producing strain and the fermentation, isolation and biological activity of A-94964. Here we report the structural elucidation of A-94964.…”

A-90289 A and B, new inhibitors of bacterial translocase I, produced by Streptomyces sp. SANK 60405

“…The resulting 16S rDNA sequence was certainly clustered into the genus Streptomyces by means of molecular phylogenetic analysis. 14 On the basis of taxonomic properties and the 16S rDNA sequence, the strain was identified as Streptomyces sp. SANK 60405.…”

“…In fact, a number of translocase I inhibitors, 1 including mureidomycins, 2 pacidamycins, 3 napsamycins, 4 liposidomycins, 5,6 tunicamycin, 7 capuramycins, 8,9 muraymycins, 10 caprazamycins, 11,12 A-102395, 13 A-94964, 14,15 muraminomicins 16 and A-97065s, 17 have been reported and focused on. The structures of liposidomycin-related compounds are composed of a uridine moiety, a 5-amino ribose moiety, a diazepanone ring system, a 3-methyl glutaric acid moiety and a fatty acid moiety.…”