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Osmolality-Independent Impact of Sodium on Glycosylation of an Fc-Fusion Protein and the Hexosamine Biosynthesis Pathway in a Chinese Hamster Ovary Cell Line
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DOI：10.1002/biot.70261.png)
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Abstract
En 中文
This study investigates the osmolality-independent effects of sodium and potassium on the glycosylation of an Fc-fusion protein and the activity of the hexosamine biosynthesis pathway in a Chinese Hamster Ovary cell line. Previous research linked low molecular weight proteoforms of this Fc-fusion protein to reduced N-glycan complexity and O-glycan site occupancy. Through a series of batch experiments, we demonstrated that increased concentrations of sodium or potassium ions led to a reduction of these proteoforms. Our findings suggest that ion availability impacts the activity of the hexosamine biosynthesis pathway, thereby enhancing the availability of uridine diphosphate N-acetylglucosamine, which is a crucial substrate for glycosylation. Notably, these changes in nucleotide sugar concentration were independent of the increased osmolality. Through supplementation of intermediates that are funneled into the hexosamine biosynthesis pathway, a link between Fc-fusion protein quality and activated sugar availability was established as each supplement that elevated nucleotide sugar concentrations reduced low molecular weight proteoforms. We hypothesize that changes in sodium and potassium concentrations lead to increased uptake of nutrients and calcium, influencing metabolic pathways and enzyme activity. Altogether, this work highlights the importance of ion balance in cell culture media development for optimizing correct glycosylation during therapeutic protein production.
Keywords:
cell culture medium
Fc-fusion protein
glycosylation
hexosamine biosynthesis pathway
osmolality
sodium chloride
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