Engineering strategies for enhanced heterologous protein production by Saccharomyces cerevisiae

Engineering strategies for enhanced heterologous protein production by Saccharomyces cerevisiae

(2024) 23:32 | Meirong Zhao, Jianfan Ma, Lei Zhang, Haishan Qi
This review discusses the engineering strategies for enhancing heterologous protein production in *Saccharomyces cerevisiae*. *S. cerevisiae* is a widely used microorganism for producing recombinant proteins due to its safety, genetic tractability, and industrial processing capabilities. The article highlights the advantages of using *S. cerevisiae* for protein production, including its ability to produce up to 49.3% of its own protein and its sophisticated eukaryotic structures that facilitate proper protein folding and post-translational modifications. The review covers several key engineering strategies to improve protein production in *S. cerevisiae*: 1. **Protein Hyperexpression Systems**: Techniques such as codon optimization, increasing gene copy numbers, and transcriptional regulation (including promoter and terminator engineering) are used to enhance protein expression levels. 2. **Protein Secretion Engineering**: Strategies like secretion signal engineering, ER folding engineering, and vesicle trafficking engineering are employed to improve protein secretion efficiency and quality. 3. **Glycosylation Pathway Engineering**: Modifying glycosylation sites and controlling N-glycan production can improve protein activity and secretion. 4. **Systems Metabolic Engineering**: Reprogramming cellular activity to reduce metabolic burden and ensure efficient protein production involves optimizing substance and energy metabolism, reducing oxidative stress, and rationally engineering metabolic pathways guided by multiomics data and constrained metabolic network models. The article also discusses the potential future directions, including the development of novel gene editing tools, the construction of highly accurate dynamic cellular models, and the utilization of third-generation feedstocks to reduce costs and align with carbon-neutral goals. Overall, the review provides a comprehensive overview of the current state and future prospects of heterologous protein production in *S. cerevisiae*.This review discusses the engineering strategies for enhancing heterologous protein production in *Saccharomyces cerevisiae*. *S. cerevisiae* is a widely used microorganism for producing recombinant proteins due to its safety, genetic tractability, and industrial processing capabilities. The article highlights the advantages of using *S. cerevisiae* for protein production, including its ability to produce up to 49.3% of its own protein and its sophisticated eukaryotic structures that facilitate proper protein folding and post-translational modifications. The review covers several key engineering strategies to improve protein production in *S. cerevisiae*: 1. **Protein Hyperexpression Systems**: Techniques such as codon optimization, increasing gene copy numbers, and transcriptional regulation (including promoter and terminator engineering) are used to enhance protein expression levels. 2. **Protein Secretion Engineering**: Strategies like secretion signal engineering, ER folding engineering, and vesicle trafficking engineering are employed to improve protein secretion efficiency and quality. 3. **Glycosylation Pathway Engineering**: Modifying glycosylation sites and controlling N-glycan production can improve protein activity and secretion. 4. **Systems Metabolic Engineering**: Reprogramming cellular activity to reduce metabolic burden and ensure efficient protein production involves optimizing substance and energy metabolism, reducing oxidative stress, and rationally engineering metabolic pathways guided by multiomics data and constrained metabolic network models. The article also discusses the potential future directions, including the development of novel gene editing tools, the construction of highly accurate dynamic cellular models, and the utilization of third-generation feedstocks to reduce costs and align with carbon-neutral goals. Overall, the review provides a comprehensive overview of the current state and future prospects of heterologous protein production in *S. cerevisiae*.
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[slides and audio] Engineering strategies for enhanced heterologous protein production by Saccharomyces cerevisiae