Pacidamycins, a novel series of antibiotics with anti-Pseudomonas aeruginosa activity. I. Taxonomy of the producing organism and fermentation.

Abstract

The pacidamycins are a new complex of nucleosidyl-peptide antibiotics with highly specific activity against Pseudomonas aeruginosa. They are produced by Streptomyces coeruleorubidus AB 1 183F-64 which was isolated from a soil sample collected at Offenburg in the FRG. The mature spore masses of the producing organism are greenish gray to blue, and the spore chains are arranged in spirals. After the structures of the pacidamycins were determined, the fermentation medium was supplemented with component amino acids. This resulted in the directed biosynthesis of several members of the complex. The overall antibiotic recovered was increased from 1~2 mg/liter to more than 100 mg/liter through a combination of strain selection, mediummanipulation and amino acid feeding experiments.

A novel assay of bacterial peptidoglycan synthesis for natural product screening

“…Then, phospho-N-acetylmuramyl-pentapeptide translocase (translocase I, MraY) catalyzes the transfer of the MurNAcpentapeptide moiety to the lipid carrier undecaprenyl phosphate to form lipid I. To date, a variety of nucleoside antibiotics have been reported as translocase I inhibitors, 5 such as mureidomycins, 6 pacidamycins, 7 napsamycins, 8 liposidomycins, 9 tunicamycin, 10 capuramycins, 11-17 muraymycins 18 and caprazamycins. 19,20 In contrast, only a few inhibitors have been reported for the steps of UDP-MurNAc-pentapeptide formation.…”

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

“…These enzymes include the first enzyme involved in the membrane stage of peptidoglycan synthesis, phospho-N-acetylmuramylpentapeptide translocase (translocase I), that catalyzes the transfer of MurNAc-pentapetide from UDP-MurNAcpentapetide to the lipid carrier undecaprenyl phosphate to form lipid I. There are several known translocase I inhibitors [1], such as mureidomycins [2], pacidamycins [3], napsamycins [4], liposidomycins [5], tunicamycin [6], capuramycins [7ϳ13], muraymycins [14] and caprazamycins [15,16]. They exhibit antimicrobial activity against various strains including multidrug-resistant ones, and show bactericidal activity [15,17,18].…”

A-90289 A and B, new inhibitors of bacterial translocase I, produced by 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.…”