基于提高蛋白在内质网中折叠效率的策略促进外源蛋白在毕赤酵母中表达水平的研究进展
Research Progress on the Strategy of Improving Protein Folding Efficiency in Endoplasmic Reticulum for Enhancing Heterologous Protein Expression Levels in Pichia pastoris

DOI: 10.12677/BP.2022.122009, PP. 81-88

Keywords: 毕赤酵母，内质网胁迫，分子伴侣，非折叠蛋白响应
Pichia pastoris, ER Stress, Chaperones, The Unfolded Protein Response

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Abstract:

新生肽在内质网中的折叠效率对于其在毕赤酵母中的高效表达是至关重要的。在内质网质量控制机制作用下，只有正确折叠的蛋白才能通过内质网通道进入随后的分泌途径，而折叠错误和折叠缓慢的多肽则被剔除出内质网，通过ERAD途径被降解。过表达外源蛋白可能造成内质网内聚集大量的未折叠蛋白，超越内质网的加工能力，从而限制其高水平表达。本文综述了通过共表达分子伴侣或UPR转录因子Hac1p促进外源蛋白表达的研究进展，以期为毕赤酵母蛋白高效表达技术的发展提供借鉴。
The efficiency of ER in folding nascent peptides is very important to increased expression of secretory proteins in Pichia pastoris. Under the machinery of quality control, only correctly folded proteins can enter the subsequent secretion pathway through the ER channel, while wrongly or slowly folded peptides will be removed from ER and degraded through ERAD pathway. Over expression of heterologous proteins may lead to the accumulation of large quantities of unfolded peptides, thus exceeding the processing capacity of ER and inhibiting high-level expression of target proteins. This paper reviews the research progress of co-expression of molecular chaperones or UPR transcription factor Hac1p to promote the secretion of heterologous proteins, providing references for the development of techniques for efficient protein expression in Pichia pastoris.

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