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用于高效生产重组蛋白的工程技术。

Engineering for efficient production of recombinant proteins.

作者信息

Yang Shuo, Song Liyun, Wang Jing, Zhao Jianzhi, Tang Hongting, Bao Xiaoming

机构信息

State Key Laboratory of Biobased Material and Green Papermaking, School of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

Center for Synthetic Biochemistry, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

出版信息

Eng Microbiol. 2023 Oct 12;4(1):100122. doi: 10.1016/j.engmic.2023.100122. eCollection 2024 Mar.

Abstract

is an excellent microbial cell factory for producing valuable recombinant proteins because of its fast growth rate, robustness, biosafety, ease of operability via mature genomic modification technologies, and the presence of a conserved post-translational modification pathway among eukaryotic organisms. However, meeting industrial and market requirements with the current low microbial production of recombinant proteins can be challenging. To address this issue, numerous efforts have been made to enhance the ability of yeast cell factories to efficiently produce proteins. In this review, we provide an overview of recent advances in engineering to improve recombinant protein production. This review focuses on the strategies that enhance protein production by regulating transcription through promoter engineering, codon optimization, and expression system optimization. Additionally, we describe modifications to the secretory pathway, including engineered protein translocation, protein folding, glycosylation modification, and vesicle trafficking. Furthermore, we discuss global metabolic pathway optimization and other relevant strategies, such as the disruption of protein degradation, cell wall engineering, and random mutagenesis. Finally, we provide an outlook on the developmental trends in this field, offering insights into future directions for improving recombinant protein production in .

摘要

由于其生长速度快、稳健性强、生物安全性高、通过成熟的基因组修饰技术易于操作,以及在真核生物中存在保守的翻译后修饰途径,是生产有价值重组蛋白的优秀微生物细胞工厂。然而,以目前微生物对重组蛋白的低产量来满足工业和市场需求可能具有挑战性。为了解决这个问题,人们已经做出了许多努力来提高酵母细胞工厂高效生产蛋白质的能力。在这篇综述中,我们概述了提高重组蛋白生产的工程学最新进展。本综述重点关注通过启动子工程、密码子优化和表达系统优化来调节转录从而提高蛋白质生产的策略。此外,我们描述了对分泌途径的修饰,包括工程化的蛋白质转运、蛋白质折叠、糖基化修饰和囊泡运输。此外,我们讨论了全局代谢途径优化和其他相关策略,如蛋白质降解的破坏、细胞壁工程和随机诱变。最后,我们对该领域的发展趋势进行了展望,为提高 中重组蛋白生产的未来方向提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b3/11611019/507702823a5c/ga1.jpg

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