Dipeptide Supplementation for Enhanced Production of Albumin-erythropoietin in CHO Cell Cultues

초록

Erythropoietin (EPO) has been used to treat anemia. Recombinant albumin-erythropoietin (Alb-EPO) fusion protein has a longer half-life than EPO. Therapeutic proteins are mostly produced in Chinese hamster ovary (CHO) cell lines 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. Among the amino acids, tyrosine (Tyr) and phenylalanine (Phe) are converted into fumarate, which is one of the intermediates in tricarboxylic acid cycle. Dipeptid 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 for the production of recombinant proteins. For that reason, Tyr-Phe dipeptide was used in this study to improve the productivity of Alb-EPO. The production of Alb-EPO was significantly enhanced by the optimal addition of Tyr-Phe. It was found that the dipeptide was more effective for the conversion into fumarate compared to each amino acid. Moreover, the reduction of intracellular NAD+/NADH implied an increased energy metabolism. In conclusion, it was apparent that the addition of Tyr-Phe dipeptide could increase the viability of CHO cells and enhance the production of recombinant Alb-EPO.