Energy metabolism in Chinese hamster ovary (CHO) cells: Productivity and beyond

Chinese hamster ovary (CHO) cell lines have been widely used to produce recombinant proteins. While the biosynthesis of recombinant proteins is energy-intensive, CHO cells exhibit inefficient metabolism, characterized by rapid conversion of glucose to lactate, possibly leading to lower cell growth and productivity of therapeutic proteins. Therefore, it is important to understand and engineer cellular metabolism to increase recombinant protein production. In this review, cellular energy metabolism of CHO cells with respect to protein synthesis is overviewed. Then, genetic and process engineering approaches to enhance metabolic efficiency are described, resulting in the improvement of cell culture performance. Finally, recent modeling technologies for understanding and predicting cellular metabolic behaviors are reviewed. These efforts will aid to further advance the biomanufacturing of therapeutic proteins.