Advancing recombinant protein production in CHO cells through metabolic engineering

Improving recombinant protein productivity in CHO cells via multi-omics data integration

Chinese hamster ovary (CHO) cells represent the dominant host system for the production of recombinant therapeutic proteins. In recent decades, extensive research has focused on process/media optimization and cell line engineering to improve both the productivity and quality of biopharmaceutical proteins produced in CHO cells. Nevertheless, the inherent complexity of biological pathways and the heterogeneous cellular responses to different environmental conditions have posed substantial challenges to traditional methodologies. Recent advances in omics technologies have enabled comprehensive characterization of CHO cell physiology, providing multidimensional molecular and phenotypic insights that facilitate the enhancement of recombinant protein production. This review first summarizes the methodologies and advances in CHO omics research, including genomics, transcriptomics, proteomics, metabolomics, and epigenomics. It then examines contemporary approaches to integrate and analyze multi-omics data in CHO cells. The review further elucidates how these multi-omics datasets can be strategically applied across various developmental stages, including cell line selection, genetic engineering, expression vector design, and bioprocess optimization. Finally, we explore the transformative potential of integrating multi-omics with artificial intelligence and discuss promising future research directions in CHO cell studies. These emerging paradigms offer novel opportunities for data-driven cell engineering and bioprocess optimization in CHO-based biomanufacturing.

Advances in Key Genetic Elements and Strategies for High-Yield Heterologous Protein Expression in Komagataella phaffii

This review summarizes recent advances in engineering key expression elements underlying heterologous protein production in K. phaffii, with particular emphasis on promoter architecture redesign, signal peptide replacement and sequence engineering, molecular chaperone co-expression, and quantitative regulation of the unfolded protein response.

Recent Advances in Engineering Microbial Cell Factories for Tryptophan-Derived Chemicals.

Tryptophan-derived metabolites are indole-containing compounds with applications in medicine, functional foods, and agriculture. Conventional production via plant extraction or chemical synthesis is often inefficient and unsustainable, prompting the development of microbial biosynthesis. In this review, these metabolites are classified based on reaction sites and the extent of l-tryptophan scaffold remodeling into side-chain-modified compounds, indole ring-functionalized compounds, oxidative coupling products, and complex indole alkaloids, providing a framework to compare biosynthetic logic across pathways. Within this context, recent advances in metabolic engineering focus on improving catalytic performance, pathway balance, and cellular robustness through enzyme engineering combined with high-throughput screening, advanced genetic tools and dynamic regulatory systems, and cellular engineering strategies such as coculture design and membrane or transporter engineering. These developments provide a basis for further integration of artificial intelligence, computational design, and bioprocess optimization to enhance the efficiency and scalability of microbial production.

Application and progress of synthetic biology technology in amino acid production.

Strategies for High-Titer and High-Quality Monoclonal Antibody Production: Cell Line Construction, Culture Medium Development, and Process Regulation in Bioreactors

This review systematically summarizes the full technological chain for efficient and high-quality mAb production, focusing on three levels: cell line construction, culture medium development, and process regulation in bioreactors, and highlights their key strategies, mechanisms, and synergistic relationships.

Precursor supply and translational machinery engineering of Saccharomyces cerevisiae for improving cellular protein content and biomass-based microbial protein bioproduction.

A multilevel engineering strategy to enhance yeast protein production by optimizing precursor supply, translation machinery, and diploid construction provides both improved protein content and key targets for breeding high-protein microbial strains.