Biotransformation of sisomicin and verdamicin by Micromonospora sagamiensis.

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.