Engineering Saccharomyces cerevisiae for efficient production of recombinant proteins

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

doi:10.1016/j.engmic.2023.100122

Engineering Microbiology ›› 2024, Vol. 4 ›› Issue (1) :100122 DOI: 10.1016/j.engmic.2023.100122

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research-article

Engineering Saccharomyces cerevisiae for efficient production of recombinant proteins

Shuo Yang ^a^,^b^,^#
, Liyun Song ^a^,^#
, Jing Wang ^b^,^c^,^d^,^#
, Jianzhi Zhao ^a
, Hongting Tang ^b^,^c^,^d^,^*
, Xiaoming Bao ^a^,^*

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Abstract

Saccharomyces cerevisiae 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 S. cerevisiae 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 S. cerevisiae.

Keywords

Saccharomyces cerevisiae / Microbial cell factory / Recombinant proteins / Transcriptional regulation / Secretory pathway / Global metabolic pathway optimization

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Shuo Yang, Liyun Song, Jing Wang, Jianzhi Zhao, Hongting Tang, Xiaoming Bao. Engineering Saccharomyces cerevisiae for efficient production of recombinant proteins. Engineering Microbiology, 2024, 4(1): 100122 DOI:10.1016/j.engmic.2023.100122

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Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Shuo Yang: Investigation, Writing - original draft. Liyun Song: Investigation, Writing - original draft. Jing Wang: Investigation, Writing - original draft. Jianzhi Zhao: Writing - review & editing. Hongting Tang: Conceptualization, Writing - original draft, Writing - review & editing. Xiaoming Bao: Conceptualization, Writing - review & editing, Funding acquisition.

Acknowledgements

This work was supported by supported by the Key innovation Project of Qilu University of Technology (Shandong Academy of Sciences) (2022JBZ01-06), the Shandong Provincial Technical Innovation Boot Program (02055183), and the Shandong Provincial Natural Science Foundation (ZR2020MC016).

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