The novel enzymatic 3''-N-acetylation of arbekacin by an aminoglycoside 3-N-acetyltransferase of Streptomyces origin and the resulting activity.
Kanamycin group antibiotics were subjected to enzymatic acetylation by a cell free extract containing an aminoglycoside 3-N-acetyltransferase, AAC(3)-X, derived from Streptomyces griseus SS-1198PR. Characterization of the incubated reaction mixtures by TLC and antibiotic assay revealed that a product retaining activity was specifically formed from arbekacin, an anti-MRSA semisynthetic aminoglycoside. The structural determination demonstrated that acetylation occurred at the 3"-amino group in arbekacin and amikacin, and at the 3-amino group in dibekacin as in the case of kanamycin. These results should reflected the effect of the (S)-4-amino-2-hydroxybutyryl side chain which is present in arbekacin and amikacin, but absent in dibekacin and kanamycin. The 3"-N-acetylation is the first finding in the enzymatic modifications of aminoglycoside antibiotics. 3"-N-Acetylarbekacin showed antibiotic activity as high as that of 2'-N-acetylarbekacin reported previously, whereas 3"-N-acetylamikacin showed no substantial activity. Thus, our results illuminated a novel aspect of arbekacin distinct from the other aminoglycosides.
Hotta
K
K
National Institute of Infectious Diseases, Tokyo, Japan.
Sunada
A
A
Ishikawa
J
J
Mizuno
S
S
Ikeda
Y
Y
Kondo
S
S
D000107:Acetylation; D000123:Acetyltransferases; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003982:Dibekacin; D000123:Acetyltransferases; C031986:arbekacin