改良毕赤酵母分泌表达外源蛋白能力的研究进展

Genetic engineering of Pichia pastoris expression system for improved secretion of heterologous proteins－A review

摘要:

摘要:巴斯德毕赤酵母(Pichia pastoris) 由于能高效表达正确折叠加工的外源蛋白而成为目前最具应用前景的表达宿主。但随着对大量不同外源蛋白在毕赤酵母中分泌表达的研究发现，并不是所有蛋白均能高效分泌表达，这严重限制了毕赤酵母这一表达系统的推广应用。相关研究发现，外源蛋白在内质网中的聚集是限制酵母分泌表达外源蛋白的主要因素，因此近年来开始尝试通过基因操作改良毕赤酵母表达外源蛋白的能力。本文综述了这一领域的研究进展。

Abstract:

Abstract:Due to the potential for producing soluble，correctly folded protein with high yield，Pichia pastoris is currently one of the most effective hosts for the expression of heterologous proteins． However，limitations of expression efficiency are often reported for many different heterologous proteins． Accumulating evidences suggest that protein folding and processing of heterologous protein is a major bottleneck during secretion process in yeast． Apart from optimization of the fermentation process，the current strategies for strain engineering for improving protein secretion are focused mainly on folding and processing，and systematic engineering by high-throughput screening for potential secretion enhancers． This article reviews the genetic engineering progresses of these aspects．