顶头孢霉遗传育种的研究进展.pdfVIP

HEREDITAS (Beijing) 2011 年 ISSN 0253-9772 顶头孢霉遗传育种研究进展 胡又佳，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：顶头孢霉是一类重要的工业微生物，其发酵产物头孢菌素 C 可用来生产 7-ACA，而后者是临床常用 抗感染药物头孢类抗生素的重要中间体。头孢菌素 C 的发酵水平决定了其下游头孢类抗生素的生产水平、 产品质量及价格，因此对顶头孢霉的菌种选育工作显得尤其迫切。随着分子生物学的发展，基因工程分子 改造在遗传育种领域发挥着越来越重要的作用。文章综述了对头孢菌素 C 的生物合成以及调控的研究进展， 并将国内外对顶头孢霉进行遗传育种的结果进行了归纳总结，提出了可以从提高头孢菌素 C 发酵水平、延 伸代谢途径等不同方面对头孢菌素 C 生物合成及调控基因，包括外源基因的导入和表达进行改造优化，并 对进一步的研究目标进行了展望，认为可以结合比较蛋白质组和基因组改组使遗传育种所获得的工程菌尽 快进入产业化。 关键词：顶头孢霉；分子育种；菌种选育；头孢菌素 C；基因工程 Research progress on strain improvement of Acremonium chrysogenum by genetic engineering HU You-Jia, ZHU Bao-Quan State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China Abstract: Acremonium chrysogenum, cephalosporin C (CPC) producing strain, is an important industrial microorganism. CPC is used to produce 7-ACA, a major intermediate for manufacturing of many first-line anti-infectious cephalosporin-antibiotics. The fermentation level of CPC determines the production, quality and cost of its downstream products. Therefore, it is necessary to develop the strains of A. chrysogenum. Along with the development of molecular biology, genetic manipulation technique is becoming more and more important in the field of molecular breeding. This paper reviews the latest research progresses on CPC biosynthesis and its regulation. Genetic manipulations of A. chrysogenum were summarized and concluded. We suggested that strain improvement of A. chrysogenum by means of induction and expression of biosynthetic and regulatory genes, a