ENZYMATIC 2'-N-ACETYLATION OF ARBEKACIN AND ANTIBIOTIC-ACTIVITY OF ITS PRODUCT

Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subje cted to enzymatic N-acetylation using a cell free extract that contain ed an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and anti biotic assay of the incubated reaction mixtures revealed that a modifi ed compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the m arked decrease in antibiotic activity. Structure determination followi ng isolation from a large scale reaction mixture showed the modified A BK to be 2'-N-acetyl ABK. In addition, 2',6'-di-N-acetyl ABK was forme d 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-ac etyl DKB. MIC determination showed antibacterial activity (1.56 simila r to 3.13 mu g/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 antibacteria l activity, compared with known N-acetylated AGs.