Engineering of protein secretion in yeast: strategies and impact on protein production |
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Authors: | Alimjan Idiris Hideki Tohda Hiromichi Kumagai Kaoru Takegawa |
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Institution: | (1) R&D Group, ASPEX Division, Research Center, Asahi Glass Co., Ltd., 1150 Hazawa-cho, Kanagawa-ku, Yokohama 221-8755, Japan;(2) Laboratory of Applied Microbiology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan |
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Abstract: | 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. |
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