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 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 approximately 3.13 micrograms/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.
Hotta
K
K
National Institute of Health, Tokyo, Japan.
Zhu
C B
CB
Ogata
T
T
Sunada
A
A
Ishikawa
J
J
Mizuno
S
S
Ikeda
Y
Y
Kondo
S
S
D000107:Acetylation; D000123:Acetyltransferases; D000215:Acylation; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D003982:Dibekacin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013302:Streptomyces; D013329:Structure-Activity Relationship
C100404:2'-N-acetylarbekacin; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003982:Dibekacin; D000123:Acetyltransferases; C031986:arbekacin