Enhanced production of albumin-erythropoietin in CHO cell cultures by using YF dipeptide

초록

Therapeutic proteins are mostly produced in Chinese hamster ovary (CHO) cell cultures which can perform correct folding and post-translational modifications. Amino acid composition of culture media is important to cell survival for the production of recombinant proteins. Dipeptides can be synthesized by chemical condensation of two amino acids. In mammalian cell cultures, dipeptides are known to improve metabolic profiles and enhance specific productivity of recombinant proteins. For that reason, tyrosine-phenylalanine (YF) dipeptide was used in this study to improve the productivity of albumin-erythropoietin (Alb-EPO). Tyrosine and phenylalanine can be converted into fumarate, which is one of the intermediates in tricarboxylic acid cycle. Viable cell density and viability were enhanced by the addition of YF dipeptide. In addition, intracellular NADH level was 61.6% higher than that of control cultures and NAD+/NADH ratio was decreased by 29.1%. Production of Alb-EPO was significantly enhanced by the optimal addition of YF dipeptide. It was found that dipeptide forms have higher solubility and the YF dipeptide was more effective for the conversion into fumarate compared to each amino acid. In conclusion, YF dipeptide was found to enhance the viability of CHO cells as well as the production of recombinant Alb-EPO.