Mattanovich Diethard, Branduardi Paola, Dato Laura, Gasser Brigitte, Sauer Michael, Porro Danilo
Department of Biotechnology, University of Natural Resources and Life Sciences, and Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Methods Mol Biol. 2012;824:329-58. doi: 10.1007/978-1-61779-433-9_17.
Recombinant protein production is a multibillion-dollar market. The development of a new product begins with the choice of a production host. While one single perfect host for every protein does not exist, several expression systems ranging from bacterial hosts to mammalian cells have been established. Among them, yeast cell factories combine the advantages of being single cells, such as fast growth and easy genetic manipulation, as well as eukaryotic features including a secretory pathway leading to correct protein processing and post-translational modifications. In this respect, especially the engineering of yeast glycosylation to produce glycoproteins of human-like glycan structures is of great interest. Additionally, different attempts of cellular engineering as well as the design of different production processes that are leading to improved productivities are presented. With the advent of cheaper next-generation sequencing techniques, systems biotechnology approaches focusing on genome scale analyses will advance and accelerate yeast cell factories and thus recombinant protein production processes in the near future. In this review we summarize advantages and limitations of the main and most promising yeast hosts, including Saccharomyces cerevisiae, Pichia pastoris, and Hansenula polymorpha as those presently used in large scale production of heterologous proteins.
重组蛋白生产是一个价值数十亿美元的市场。新产品的开发始于生产宿主的选择。虽然不存在适用于每种蛋白质的单一完美宿主,但已经建立了从细菌宿主到哺乳动物细胞的多种表达系统。其中,酵母细胞工厂兼具单细胞的优势,如生长迅速和易于基因操作,以及真核生物的特性,包括可导致正确蛋白质加工和翻译后修饰的分泌途径。在这方面,特别是对酵母糖基化进行工程改造以生产具有类人聚糖结构的糖蛋白备受关注。此外,还介绍了细胞工程的不同尝试以及旨在提高生产力的不同生产工艺设计。随着更廉价的新一代测序技术的出现,专注于基因组规模分析的系统生物技术方法将在不久的将来推动并加速酵母细胞工厂以及重组蛋白生产过程的发展。在本综述中,我们总结了主要且最具潜力的酵母宿主的优势和局限性,包括目前用于大规模生产异源蛋白的酿酒酵母、巴斯德毕赤酵母和多形汉逊酵母。