Hotta K, Sunada A, Ishikawa J, Mizuno S, Ikeda Y, Kondo S
National Institute of Infectious Diseases, Tokyo, Japan.
J Antibiot (Tokyo). 1998 Aug;51(8):735-42. doi: 10.7164/antibiotics.51.735.
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.
卡那霉素类抗生素由含有源自灰色链霉菌SS - 1198PR的氨基糖苷3 - N - 乙酰转移酶AAC(3)-X的无细胞提取物进行酶促乙酰化。通过薄层色谱法（TLC）和抗生素测定对孵育后的反应混合物进行表征，结果显示，一种保留活性的产物是由阿贝卡星（一种抗耐甲氧西林金黄色葡萄球菌的半合成氨基糖苷）特异性形成的。结构测定表明，乙酰化发生在阿贝卡星和阿米卡星的3''-氨基上，以及双去氧卡那霉素的3 - 氨基上，如同卡那霉素的情况一样。这些结果应反映了存在于阿贝卡星和阿米卡星中但不存在于双去氧卡那霉素和卡那霉素中的(S)-4 - 氨基 - 2 - 羟基丁酰侧链的作用。3''-N - 乙酰化是氨基糖苷类抗生素酶促修饰中的首次发现。3''-N - 乙酰阿贝卡星显示出与先前报道的2'-N - 乙酰阿贝卡星一样高的抗生素活性，而3''-N - 乙酰阿米卡星则没有显著活性。因此，我们的结果揭示了阿贝卡星与其他氨基糖苷类不同的一个新方面。
