Engineering of protein secretion in yeast: strategies and impact on protein production

• Published in: Applied microbiology and biotechnology Vol. 86; no. 2; pp. 403 - 417
• Main Authors: Idiris, Alimjan, Tohda, Hideki, Kumagai, Hiromichi, Takegawa, Kaoru
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-03-2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biotechnology; Fermentation; Fundamental and applied biological sciences. Psychology; Genetic Engineering; Glycoproteins; Humans; Industrial production; Life Sciences; Metabolic Networks and Pathways - genetics; Methods. Procedures. Technologies; Microbial Genetics and Genomics; Microbiology; Microorganisms; Mini-Review; Optimization; Proteases; Protein engineering; Protein folding; Quality control; R&D; Recombinant Proteins - secretion; Research & development; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Studies; Yeast; Yeasts; Membrane trafficking; Glycosylation; Protein folding; Protease; Secretion pathway; Yeast secretion system; Protein engineering; Yeast; Enzyme; Secretion; Refolding; Protein; Peptidases; Production; Hydrolases; Membrane
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-010-2447-0

Yeasts combine the ease of genetic manipulation and fermentation of a microorganism with the capability to secrete and modify foreign proteins according to a general eukaryotic scheme. Their rapid growth, microbiological safety, and high-density fermentation in simplified medium have a high impact particularly in the large-scale industrial production of foreign proteins, where secretory expression is important for simplifying the downstream protein purification process. However, secretory expression of heterologous proteins in yeast is often subject to several bottlenecks that limit yield. Thus, many studies on yeast secretion systems have focused on the engineering of the fermentation process, vector systems, and host strains. Recently, strain engineering by genetic modification has been the most useful and effective method for overcoming the drawbacks in yeast secretion pathways. Such an approach is now being promoted strongly by current post-genomic technology and system biology tools. However, engineering of the yeast secretion system is complicated by the involvement of many cross-reacting factors. Tight interdependence of each of these factors makes genetic modification difficult. This indicates the necessity of developing a novel systematic modification strategy for genetic engineering of the yeast secretion system. This mini-review focuses on recent strategies and their advantages for systematic engineering of yeast strains for effective protein secretion.