毕赤酵母外源蛋白分泌及折叠途径的改良进展

Improvement of Heterologous Protein Secretion and Folding Pathways of Pichia pastoris

工业、农业和医药等领域常用的活性蛋白和工业酶大多数通过异源表达系统获得。毕赤酵母(Pichia pastoris)是优秀的外源蛋白表达宿主之一,以毕赤酵母为宿主的表达系统具有遗传稳定性好、翻译后修饰、蛋白表达和分泌水平高及生产成本低等优点,但在高效表达过程中外源蛋白过量聚集会导致目标蛋白不能正确折叠和有效分泌,从而影响蛋白表达水平。概述了通过信号肽优化、分子伴侣优化以及融合蛋白表达等分泌及折叠途径的改良,从而促进外源蛋白高效表达的研究进展。

Most of the active proteins and industrial enzymes commonly used in industry,agriculture and medicine are obtained through heterologous expression systems.Pichia pastoris is one of the excellent hosts for expressing heterologous proteins.This expression system has the advantages including good genetic stability,high protein expression and secretory level,post-translational modification system,and low cost etc.However,excessive aggregation of heterologous proteins usually leads to incorrect fold and ineffective secretion of the target proteins,thus decling protein expression level.This paper reviewed the progress in the study on exogenous protein expression in Pichia pastoris by engineering the secretion and folding pathways such as signal peptide optimization,chaperone optimization and fusion protein expression.