Role of Chinese hamster ovary central carbon metabolism in controlling the quality of secreted biotherapeutic proteins

Abstract

Recombinant proteins produced via Chinese hamster ovary (CHO) cell cultures constitute the majority of biotherapeutics on the market. The ability of these cultures to consistently perform human-like post-translational modifications, mainly glycosylation, is paramount to product quality. Although much research has focused on understanding enzymatic function and regulation in the glycosylation pathways of CHO cells, central carbon metabolism also plays an important role in determining protein quality by supplying nucleotide sugar precursors and generating inhibitory byproducts that affect protein glycosylation. Central carbon metabolism also generates reductant molecules that can promote disulfide bond cleavage during harvest, influencing the quality of the product. Through understanding CHO cell central carbon metabolism, host cell engineering strategies and process modifications have been developed to improve protein quality. This review highlights these advances and presents opportunities for future research toward understanding the role of central metabolism in controlling the quality of biotherapeutic proteins.