Intracellular metabolic flux analysis of CHO cells supplemented with wheat hydrolysates for improved mAb production and cell-growth

BACKGROUNDIn the production of therapeutic proteins using Chinese hamster ovary (CHO) cell culture, the compositional variability in raw materials is often poorly understood. To elucidate the effects of raw material variability in regulating the intracellular metabolic pathways, plant-derived supplements of wheat hydrolysates were employed as a model system of raw materials having high compositional variability. The intracellular metabolic fluxes of antibody-producing GS-CHO cells supplemented with different lots of wheat hydrolysates were quantified using the techniques of flux balance analysis (FBA). RESULTSThe examination of the metabolic flux clearly illustrated several unique metabolic features. Specifically, under the given environmental conditions induced by the variability of the different wheat hydrolysate lots, the serine and glycine metabolism could be linked to improved cell growth, while the elevated levels of the anaplerotic reaction and the TCA cycle could be related to the increased specific antibody production. Multivariate data analysis revealed the detailed metabolic regulations of a GS-CHO cell line in response to the compositional variability of the given raw materials. The study result can be used for targeted optimization of cell growth and monoclonal antibody production. CONCLUSIONMetabolic flux analysis coupled with multivariate data analytics unravel the complicated effects of raw material variability on the cellular metabolism, and hence improve the overall productivity of an antibody-producing CHO cell culture. (c) 2014 Society of Chemical Industry