【摘要】 <正> β—内酰胺系列抗菌素抗菌谱广、疗效高、毒副作用小,国际上研究与应用日渐广泛深入。头孢氨苄(Cephalexin)是重要的半合成抗菌素之一,由头孢霉素母核7—氨基脱乙酰氧基头孢烷酸(简称7-ADCA)和侧链结构物苯甘氨酸或其甲酯(PGME)经酰化而生成。酰化有化学法和酶法两种。采用青霉素G酰化酶或a—氨基酸酯酶或,a—氨酰转移酶的酶法,具有工艺操作简单、无需基团保护、环境污染轻等优点。继日本人于70年代初试验成功酶法之后,80年代初我们开展了这方面研究。制备方面,胞外酶优于胞内酶;使用方面,固定化酶优于固定化细胞。在用具有青霉素G酰化酶活性的固定化大肠杆菌(Escherichia coli)细胞合成头孢氨苄的基础上,又研究了用固定化巨大芽孢杆菌(Bacillus megaterium)BP931胞外青霉素G酰化酶酰化合成头孢氨苄的条件。本文报道这一研究结果。更多还原

【Abstract】 Cephalexin was synthesized by γ-alumina-immobilized form the extracellular penicillin G acylase of Bacillus megaterium with 7-aminodeacetoxycephalosporanic acid as acyl acceptor and D-phenyglycine methyl ester as acyl donor. The optimum temperature was 10-35℃, depending on designed time for synthesis. The initial reaction mixture contained 2% the acyl acceptor, 4% the acyl donor and 24IU of immobilized enzyme per milliliter. After stirring 5h at pH 6.5 and 10℃, 80% of the acyl acceptor was acylated. The conversion rate of 7-aminodeacetoxycephalosporanic acid was 86% with 85% yield of cephalexin on pilot plantscale. Enzymatic synthesis was markedly inhibited by 7-phenylacetamido-aminodea-cetoxycephalosporanic acid, phenylacetic acid and phenoxyacetic acid.更多还原