Application of Dipeptide for Enhanced Production of Albumin-erythropoietin in CHO Cell Cultures

초록

Chinese hamster ovary (CHO) cells are the mostly favored host cell line for the industrial production of recombinant proteins. Dipeptide is composed of two amino acids by dehydration. Many studies have been reported on the effects of dipeptide for protein production in mammlian cell cultures. In this study, in order to improve the production of albuminerythropoietin (Alb-EPO), tyrosine-phenylalanine (YF) dipeptide was supplemented in recombinant CHO cell cultures. Addition of YF dipeptide is known to activate tricarboxylic acid (TCA) cycle due to the increase of fumarate. Viable cell density and viability were enhanced by the addition of YF dipeptide. Intracellular NADH level was 61.6% higher than that of control cultures and NAD+/NADH ratio was decreased by 29.1%. Futhermore it was found that the productivity of Alb-EPO was improved 27.2% compared to that of control. YF dipeptide was more effective in improving TCA cycle and enhancing the production of Alb-EPO in comparison with the addition of each amino acid. Production of recombinant proteins from CHO cells was improved by supplementing dipeptide through the conversion into intermediates of TCA cycle. Therefore, it is clear that the use of dipeptide could be beneficial for the industrial production of therapeutic proteins.