Metabolic Profiling of CHO-K1 Cells Adapted to Glutamine-Free Media

Chinese hamster ovary (CHO) cells are the workhorses for the industrial production of biopharmaceuticals. Typically CHO cells grow on a glutamine supplemented media, which improves cell growth and cell viability. However, glutamine supplementation results in ammonia secretion, which is detrimental to quality-determining parameters of biopharmaceuticals. Here, we investigated the system-wide response of CHO cells to glutamine supplemented and glutamine free media.

We ran batch fermentations to collect multi-omics data of the transcriptome, proteome and metabolome across the life cycle and used flux balance analysis (FBA) to gain a holistic description. Cells adapted to low glutamine concentration in the media showed increased glutamate and aspartate uptake rates, as well as enhanced growth properties such as an increased viable cell density. These experimental results were in good agreement with the predictions of FBA performed in the genome-scale metabolic model of CHO.