后基因组时代的丝状真菌基因组学与代谢工程

doi:10.3724/SP.J.1005.2011.01067

遗传 ›› 2011, Vol. 33 ›› Issue (10): 1067-1078.doi: 10.3724/SP.J.1005.2011.01067

后基因组时代的丝状真菌基因组学与代谢工程

陈献忠^{1, 2}, 沈微^{1, 2}, 樊游^{1, 2}, 王正祥^{1, 2}

1. 江南大学工业生物技术教育部重点实验室, 无锡 214122 2. 江南大学生物工程学院生物资源与生物能源研究中心, 无锡 214122

收稿日期:2011-04-19 修回日期:2011-05-17 出版日期:2011-10-20 发布日期:2011-10-25
通讯作者: 陈献忠 E-mail:cxzcool2000@yahoo.com.cn
基金资助:
国家自然科学基金项目(编号：21006039)和国际科技合作重点项目(编号：2009DFA31300)资助

Genomics and metabolic engineering of filamentous fungi in the post-genomics era

CHEN Xian-Zhong^1,2, SHEN Wei^1,2, FAN You^1,2, WANG Zheng-Xiang^1,2

1. Key Lab of Industrial Biotechnology, Education Ministry, Jiangnan University, Wuxi 214122, China 2. Research Center of Bioresource and Bioenergy, School of Biotechnology, Jiangnan University, Wuxi 214122, China

Received:2011-04-19 Revised:2011-05-17 Online:2011-10-20 Published:2011-10-25
Contact: CHEN Xian-Zhong E-mail:cxzcool2000@yahoo.com.cn

摘要/Abstract

摘要： 丝状真菌不仅是传统发酵工业中抗生素、酶制剂和有机酸的主要生产者, 而且也是代谢工程育种中异源蛋白表达的重要细胞工厂。丝状真菌的遗传修饰和代谢工程研究是现代工业生物技术领域最具活力的研究方向之一。特别是与细菌和酵母相比, 丝状真菌在细胞生长、营养需求、环境适应性、翻译后修饰、蛋白分泌能力和生物安全性等方面具有显著的优势。文章综述了丝状真菌作为异源蛋白表达系统在基因组学技术研究和代谢工程研究方面的最新进展。作者在分析丝状真菌基因组结构、特点的基础上, 阐述了比较基因组学、蛋白质组学、转录组学和代谢组学等对丝状真菌的代谢途径重构、新型蛋白挖掘和代谢工程育种中的作用和意义。另一方面, 作者分析了丝状真菌在表达外源蛋白时遇到的瓶颈问题, 总结了丝状真菌代谢工程育种中的常用策略包括异源基因的融合表达、反义核酸技术、蛋白分泌途径改造、密码子优化和蛋白酶缺陷宿主的选育等技术和手段。最后, 对该领域的发展趋势进行了展望。

关键词: 丝状真菌, 基因组学, 代谢工程, 异源蛋白, 细胞工厂

Abstract: Filamentous fungi are used in a variety of industrial processes including the production of primary metabolites (e.g., organic acid, vitamins, and extracellular enzymes) and secondary metabolites (e.g., antibiotics, alkaloids, and gibberellins). Moreover, filamentous fungi have become preferred cell factories for production of foreign (heterologous) proteins in biotechnology in recent years. Compared to bacterial and yeast hosts, filamentous fungi showed predominant features such as the ability of growing on rather simple and inexpensive substrates, producing and secreting exceptionally large amounts of proteins, post-translational modifications, and GRAS (generally regarded as safe) approval. Therefore, the exploration of filamentous fungi has been attractive recently. This review summarizes the recent development in genomics, comparative genomics, transcriptomics, proteomics and metabolomics of filamentous fungi, and describes their applications and functions in reconstruction of metabolic network, discovery of novel proteins and genes, investigation of cell physiological and biochemical reactions, and strain breeding. This review also analyzes the bottlenecks of heterologous protein expression in filamentous fungi. Furthermore, special emphasis is given on the strategies for improving the protein production, including fusion expression of heterologous proteins, RNAi technology, manipulations of secretion pathways, codon optimization of foreign genes, and screening of protease mutants. Lastly, this review proposes the future direction of meta-bolic engineering of filamentous fungi.

Key words: filamentous fungi, genomics, metabolic engineering, heterologous proteins, cell factory

陈献忠，沈微，樊游，王正祥. 后基因组时代的丝状真菌基因组学与代谢工程[J]. 遗传, 2011, 33(10): 1067-1078.

CHEN Xian-Zhong, CHEN Wei, FAN Liu, WANG Zheng-Xiang. Genomics and metabolic engineering of filamentous fungi in the post-genomics era[J]. HEREDITAS, 2011, 33(10): 1067-1078.

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后基因组时代的丝状真菌基因组学与代谢工程

Genomics and metabolic engineering of filamentous fungi in the post-genomics era

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