A-102395, a New Inhibitor of Bacterial Translocase I, Produced by Amycolatopsis sp. SANK 60206

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 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 IC 50 value of 11 nM, but possesses no antimicrobial activity against various strains tested.

Characterization of LipL as a Non-heme, Fe(II)-dependent α-Ketoglutarate:UMP Dioxygenase That Generates Uridine-5′-aldehyde during A-90289 Biosynthesis

“…SANK 62799 (8), and A-102395 from Amycolatopsis sp. SANK 60206 (9). However, despite several notable structural variations, the last three of these four groups share one signature feature that is critical for biological activity: a uracil-containing nucleoside component that consists of a high-carbon furanoside, wherein the typical ribosyl moiety is replaced by a hexafuranoside (C6), heptafuranoside (C7), or, in the case of tunicamycin, an undecafuranoside (C11) ( Fig.…”

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

“…Neither HMBC correlation from H-2¢¢¢ (d H 4.16) nor H-3¢¢¢ (d H 5.33) to C-1¢¢¢ carbonyl carbon was observed on the partial structure elucidated as the diazepanone ring system. However, the carbonyl carbon of d C 171.5 was assigned to the C-1¢¢¢ position because the 13 The connectivities of these partial structures were revealed by the correlations in DQF-COSY and HMBC spectrum, as shown in Figure 3 Thus, the core structure of 1 was established as illustrated in Figure 3.…”

“…All the NMR spectra were recorded at 300 K on a DRX 500 spectrometer (Bruker BioSpin, Kanagawa, Japan) equipped with a cryogenic probe operating at 500 MHz for 1 H and 125 MHz for 13 C NMR spectra. The samples for NMR characterization were dissolved in methanol-d 4 /dimethylsulfoxide-d 6 /deuterium oxide (10:10:1).…”

“…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.…”