Antimicrobial agents.

Gentamicin Clb is 6'-N-methylgentamicin Cia. This antibiotic is coproduced, as one of minor components, in the standard gentamicin fermentation. Kershner (Ph.D. thesis, Rutgers University, New Brunswick, N.J., 1971) first described its presence in trace amounts in gentamicin preparations. Daniels and co-workers (2) reported its isolation, purification, and characterization from fermentation both of a Micromonospora purpurea mutant, which produced gentamicin Cla as a major product and gentamicin Clb as a minor product. Unlike the parental gentamicin-producing strain, however, the mutant strain did not produce any detectable amounts of gentamicins C, and C2. Okachi and co-workers (6) reported on the isolation of sagamicin from Micromonospora sagamiensis, which was found to be identical to gentamicin C2b (2). Transformation of gentamicin Cla or sisomicin to gentamicin C2b has been achieved by an M. purpurea-blocked mutant, SC 1124 (B. K. Lee and R. G. Condon, unpublislhed data). Whereas the transformation of gentamicin C,a to C2b would require a single enzymatic reaction, 6'-N-methylation, that of sisomicin to C2b would require (4'-5')-reduction as an additional enzymatic reaction. Micromonospora rhodorangea NRRL 5326 has been shown to produce antibiotic G-418 (6'-C-methylgentamicin X2). Since it was thought this strain might lack the (4'-5')-reduction activity, we chose this strain rather than M. purpurea SC 1124 to transform sisomicin to 6'-N-methylsisomicin (antibiotic G-52[1,5]. Unexpectedly, however, M. rhodorangea.5326, like M. purpurea 1124, yielded gentamicin C2b (Fig. 1). A 10-liter preparative fermentation was carried out to study the M. rhodorangea strain-mediated biotransformation in detail. The results of the examination of the biotransformation products are reported in this paper. MATERIALS AND METHODS