《生命科学》 2011, 23(9): 912-916

发酵生产7-ACA基因工程菌的构建

胡又佳^*，刘　艳，朱宝泉

(上海医药工业研究院，创新药物与制药工艺国家重点实验室，上海 200437)

摘　要：摘　要：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。
关键词：7-ACA；顶头孢霉；头孢菌素C；合成生物学；基因工程

Construction of an engineering Acremonium chrysogenum for fermentation

HU You-Jia^*， LIU Yan， ZHU Bao-Quan

(State Key Laboratory of New Drug and Pharmaceutical Process， Shanghai Institute of Pharmaceutical Industry， Shanghai 200437， China)

Abstract: Abstract: Cephalosporins antibiotics are the most widely used anti-infectious drugs in clinic. The important intermediate for cephalosporins antibiotics， 7-aminocephalosporanic acid (7-ACA)， is produced by semi-chemical synthesis or two-step immobilized enzymatic transformation from cephalosporin C， the metabolites of Acremonium chrysogenum， in industry. We report here that on the basis of understanding the cephalosporin C biosynthesis and establishing the genetic modification of A. chrysogenum， three different cephalosporin C acylase expression cassettes were introduced into A. chrysogenum upon the advance of synthetic biology. After analysis of the engineering strains metabolites， the best expression cassette was chosen followed by optimization of traditional fermentation process. In conclusion， a high-yield engineering A. chrysogenum for direct fermentation of 7-ACA was obtained.
Key words: 7-ACA; Acremonium chrysogenum; cephalosporin C; synthetic biology; genetic engineering