MICROBIAL SEMI-SYNTHESIS OF AMINOGLYCOSIDIC ANTIBIOTICS BY MUTANTS OF S. RIBOSIDIFICUS AND S. KANAMYCETICUS

The Journal of Antibiotics
1973.0

Abstract

During studies on the biosynthesis of aminoglycosidic antibiotics, we isolated deoxystreptamine-negative mutants of Streptomyces ribosidificus (named AF-1 strain) and Streptomyces kanamyceticus. The AF-1 strain of S. ribosidificus produced new ribostamycin analogs (4, 5, 6) by adding deoxystreptamine analogs (1-N-methyl deoxystreptamine, streptamine, myo-inosadiamine-1,3), and ribostamycin (9) and 3',4'-dideoxy ribostamycin (10) by adding neamine and 3',4'-dideoxyneamine, respectively. These ribostamycin analogs were isolated, and their physicochemical properties (m.p., specific rotation, TLC Rf value, NMR, mass spectrum) and bioactivities were determined. For the deoxystreptamine-negative mutant of S. kanamyceticus, adding 1-N-methyl deoxystreptamine (1) and myo-inosadiamine-1,3 (3) yielded two new kanamycin analogs (12, 13), whose structures were identified by NMR and acid hydrolysis, while other deoxystreptamine analogs such as streptamine, N,N'-diacetyl deoxystreptamine and N,N'-dimethyl deoxystreptamine gave no bioactive substance. Detailed procedure on fermentation, isolation, physico-chemical properties and structure determination will be published in another paper.

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