Hu You-Jia, Zhu Bao-Quan
Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
Yi Chuan. 2011 Oct;33(10):1079-86. doi: 10.3724/sp.j.1005.2011.01079.
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, as well as exogenous genes, and further optimization 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 shuffling with molecular breeding could lead the achievements close to industry promptly.
产黄顶头孢霉是生产头孢菌素C(CPC)的菌株,是一种重要的工业微生物。CPC用于生产7-氨基头孢烷酸(7-ACA),它是制造许多一线抗感染头孢菌素抗生素的主要中间体。CPC的发酵水平决定了其下游产品的产量、质量和成本。因此,有必要对产黄顶头孢霉进行菌株改良。随着分子生物学的发展,基因操作技术在分子育种领域变得越来越重要。本文综述了CPC生物合成及其调控的最新研究进展。总结并归纳了产黄顶头孢霉的基因操作。我们建议通过生物合成和调控基因以及外源基因的诱导和表达对产黄顶头孢霉进行菌株改良,并进一步优化,这可应用于提高CPC产量、延长代谢途径等不同方面。还提出了该领域的未来发展方向。我们认为将比较蛋白质组学和基因组改组与分子育种相结合能够迅速使成果接近工业化。