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。
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 cepha-losporin-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, as well as exogenous genes, and further optimi-zation could be applied to different aspects including CPC production enhancement and metabolic pathway elongation, etc. Future direction of this field is also proposed. We believed that incorporation of comparative proteomics and genomic shuf-fling with molecular breeding could lead the achievements close to industry promptly.
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