Influence of ammonium on growth, metabolism, and productivity of a continuous suspension Chinese hamster ovary cell culture.
A recombinant DNA Chinese hamster ovary (CHO) cell line which produces tissue-type plasminogen activator (t-PA) was cultivated continuously in suspension with a constant dilution rate of 0.5 day-1. The cultivation consisted of four phases with four different ammonium chloride concentrations (0, 2.5, 5, and 7.5 mM) in the feed medium, causing a reactor ammonium concentration of up to 8 mM. Cell growth was not inhibited by these high ammonium concentrations, as cell densities of around 2.3 x 10(6) cells mL-1 were established. In contrast, the production of t-PA was reduced under high ammonium concentration. The decrease in specific t-PA production could be due to either a negative ammonium influence on productivity or a limitation of medium components, e.g., amino acids. Cell metabolism was changed under high ammonium concentrations, seen most clearly by a decrease in specific ammonium production by a factor of 8 and an increase in specific alanine production of 30%.
Hansen
H A
HA
Department of Biotechnology, Technical University of Denmark, Lyngby.
Emborg
C
C
D000596:Amino Acids / Q000096:biosynthesis; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis*; D013535:Suspensions; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*
D000596:Amino Acids; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; D013535:Suspensions; D010959:Tissue Plasminogen Activator