Enzymatic 2'-N-Acetylation of Arbekacin and Antibiotic Activity of Its Product

Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibioti...

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Bibliographic Details
Published in:Journal of antibiotics 1996/05/25, Vol.49(5), pp.458-464
Main Authors: HOTTA, KUNIMOTO, ZHU, CHUN-BAO, OGATA, TETSU, SUNADA, AISUKO, ISHIKAWA, JUN, MIZUNO, SATOSHI, IKEDA, YOKO, KONDO, SHINICHI
Format: Article
Language:English
Subjects:
Acetylation
Acetyltransferases
Acylation
Aminoglycosides
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - isolation & purification
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Dibekacin - analogs & derivatives
Dibekacin - chemistry
Dibekacin - isolation & purification
Dibekacin - metabolism
Dibekacin - pharmacology
Medical sciences
Microbial Sensitivity Tests
Molecular Structure
Pharmacology. Drug treatments
Streptomyces
Streptomyces kasugaensis
Structure-Activity Relationship
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Summary:Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibiotic assay of the incubated reaction mixtures revealed that a modified compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the marked decrease in antibiotic activity. Structure determination following isolation from a large scale reaction mixture showed the modified ABK to be 2'-N-acetyl ABK. In addition, 2', 6'-di-N-acetyl ABK was formed as a minor product. The same conversion also occurred with dibekacin (DKB) resulting in the formation of 2'-N-acetyl DKB and 2', 6'-di-N-acetyl DKB. MIC determination showed antibacterial activity (1.56-3.13 μg/ml) of 2'-N-acetyl ABK against a variety of organisms. By contrast, 2'-N-acetyl DKB showed no substantial antibiotic activity. We believe 2'-N-acetyl ABK has the highest and broadest antibacterial activity, compared with known N-acetylated AGs.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.49.458