Verdamicin

Abstract: The mechanism of self-defence against their own product was studied in five aminoglycoside-producing Micromonospora (M.) species: M. grisea (verdamicin producer); M. inyoensis (sisomicin producer); M. sagamiensis (sagamicin producer); M. rhodorangea (antibiotic G-418 producer) and M. zionensis (antibiotic G-52 producer). Analysis of cell-free extracts of these organisms showed that they were devoid of modification enzymes specific for aminoglycosides. They contained, however, high-level resistant ribosomes. Mixed subunit exchange experiments of ribosomes from the producer strains and from a sensitive non-producing species (M. melanosporea) demonstrated that it is the 30S subunit which confers resistance.

Abstract: The resting cells of a 2-deoxystreptamine idiotrophic mutant of Micromonospora sagamiensis were found to transform sisomicin into gentamicin C1a and sagamicin. The biotransformation products were isolated by a combination of ion exchange and carbon column chromatographic procedures, and properly identified. Antibiotic G-52 (6'-N-methylsisomicin) was not detected in the transformation products. Gentamicin C1a was formed at an early stage of the biotransformation, followed by sagamicin formation. The (4', 5')-reduction of sisomicin may occur first, followed by 6'-N-methylation. By use of a similar procedure, it was demonstrated that verdamicin was transformed into gentamicin C2a (the 6'-C epimer of gentamicin C2), C2, and then C1. Carbon TLC clearly separated gentamicin C2a, C2, and verdamicin. In this biotransformation, the (4', 5')-reduction of verdamicin occurred first, followed by 6'-C-epimerization, and then 6'-N-methylation. In contrast with M. sagamiensis, M. zionensis NRRL5466 and M. inyoensis NRRL3292 did not possess any detectable activity of the (4', 5')-reduction of sisomicin or verdamicin. Alternatively, NRRL5466 transformed sisomicin into antibiotic G-52, and verdamicin into a new antibiotic, VF3-1. The antibiotic VF3-1 was suggested as 6'-N-methylverdamicm by chromatographic and mass spectrum data. The implications of these findings were discussed in relation to sagamicin biosynthesis in M. sagamiensis.

Abstract: The in vitro activities of verdamicin and gentamicin were studied in parallel against 1,049 bacterial isolates. Verdamicin demonstrated activity similar to that of gentamicin against members of the family Enterobacteriaceae and against Pseudomonas aeruginosa at 2 and 8 μg/ml, respectively. Proteus rettgeri and Providencia stuartii were notably more susceptible to verdamicin. The new aminoglycoside was also highly active against staphylococci but was not effective against group D streptococci.

Abstract: A novel composition having antibiotic activity is produced by fermentation of the new species of microorganism, Micromonospora grisea. The antibiotic complex is composed of four components, Verdamicin I, sisomicin, Antibiotic G-418, and gentamicin A, of which Verdamicin I is a novel basic antibiotic possessing a broad antibacterial spectrum. The other components have been produced previously.