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头孢菌素类抗生素是临床用途最广的抗感染药物,其工业生产的重要中间体7-氨基头孢烷酸(7-ACA)采用顶头孢霉发酵产物头孢菌素C为前体,通过化学合成或两步酶法获得。介绍了在了解头孢菌素C生物合成的前提下,在建立了顶头孢霉的遗传改造基础上,运用合成生物学的知识,在头孢菌素C产生菌顶头孢霉中分别构建了三个头孢菌素C酰化酶的表达框架,通过发酵产物的分析并优选表达框架后,再采用传统发酵工艺的优化获得了一株可以直接发酵7-ACA的高产顶头孢霉工程菌。
Cephalosporins antibiotics is the most widely used clinical anti-infective drugs, its industrial production of an important intermediate 7-amino-cephalosporanic acid (7-ACA) Cephalosporium acuminatum fermentation product cephalosporin C as a precursor by chemical synthesis Or two-step enzyme method. Based on the understanding of the cephalosporin C biosynthesis, based on the genetic modification of Cephalosporium acremonium, three cephalosporins were constructed in cephalosporin C-producing Cephalosporium acremonium using the knowledge of synthetic biology After the analysis of the fermentation product and expression of the framework, the strain Cephalosporium acremonium that can directly ferment 7-ACA was obtained by the optimization of the traditional fermentation process.