MUTATIONAL BIOSYNTHESIS OF BUTIROSIN ANALOGS: III. 6'-N-METHYLBUTIROSINS AND 3', 4'-DIDEOXY-6'-C-METHYLBUTIROSINS, NEW SEMISYNTHETIC AMINOGLYCOSIDES

Two pairs of butirosin analogs were isolated from the fermentation broths obtained by cultivating a neamine-negative mutant of the butirosin-producing organism Bacillus circulars in the medium supplemented with 6'-N-methylneamine and gentamine C2, respectively. These antibiotics were characteri...

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Bibliographic Details
Published in:Journal of antibiotics 1978, Vol.31(10), pp.1039-1045
Main Authors: TAKEDA, KATSUO, KINUMAKI, AKIO, OKUNO, SATOSHI, MATSUSHITA, TADAHIRO, ITO, YUKIO
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - biosynthesis
Bacillus - metabolism
Bacteria - drug effects
Butirosin Sulfate - biosynthesis
Butirosin Sulfate - pharmacology
Chemical Phenomena
Chemistry
Molecular Conformation
Mutation
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Summary:Two pairs of butirosin analogs were isolated from the fermentation broths obtained by cultivating a neamine-negative mutant of the butirosin-producing organism Bacillus circulars in the medium supplemented with 6'-N-methylneamine and gentamine C2, respectively. These antibiotics were characterized as 6'-N-methylbutirosins A and B (NMB-A & NMB-B), and 3', 4'-dideoxy-6'-C-methylbutirosins A and B (DCB-A & DCB-B), respectively, by chemical and spectroscopic studies. NMB-A and NMB-B exhibited broad-spectrum antibacterial activities with in vitro potency similar to or slightly less than that for butirosin A, but with greater activities against butirosin-resistant strain which contains acetylating enzyme AAC- (6')-I. The activities of NMB-A and NMB-B against Pseudomonas aeruginosa strains were relatively weak. DCB-B had broad-spectrum activity, and exhibited greatly improved activity against butirosin-resistant organisms which contain acetylating enzymes AAC(6')-I and AAC(6')-IV, and phosphorylating enzyme APH(3')-II. These new butirosin analogs were also active against some of the clinical isolates resistant to butirosins, dibekacin and/or gentamicin.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.31.1039