MUTATIONAL BIOSYNTHESIS OF BUTIROSIN ANALOGS
II. 3', 4'-DIDEOXY-6'-N-METHYLBUTIROSINS, NEW SEMISYNTHETIC AMINOGLYCOSIDES
1978 Volume 31 Issue 10 Pages 1031-1038
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1978 Volume 31 Issue 10 Pages 1031-1038
A pair of new butirosin analogs was isolated from the fermentation broth obtained by cultivating a neamine-negative mutant of the butirosin-producing organism Bacillus circulans in the medium supplemented with 6'-N-methylgentamine C1a. These antibiotics were characterized and elucidated as 3', 4'-dideoxy-6'-N-methylbutirosins A and B (DMB-A & DMB-B), by chemical and spectroscopic studies. DMB-A and DMB-B exhibited broad-spectrum antibacterial activities with in vitro potency similar to or slightly less than that for the butirosin A, with the exception of strains of Pseudomonas aeruginosa and Serratia marcescens against which they exhibited activities equal to or slightly greater than that for butirosin A. As expected, they exhibited stronger activities against butirosin-resistant organisms which contain acetylating enzymes AAC(6')-I and AAC(6')-IV, and phosphorylating enzyme APH(3')-II. They were also active against some of the clinical isolates resistant to butirosins, dibekacin and/or gentamicin. The acute intravenous toxicity in mice of the DMB complex (B: 70-80%) was somewhat less than that of the butirosin A.
