Expression of carbamoyl phosphate synthetase I and ornithine transcarbamoylase genes in Chinese hamster ovary dhfr-cells decreases accumulation of ammonium ion in culture media

Hyo Soon Park, Ik Hwan Kim, Ick Young Kim, Ki Ho Kim, Hong Jin Kim

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32 Citations (Scopus)


Ammonium ion accumulation in mammalian cell culture media causes toxicity which inhibits cell growth and productivity. To reduce the level of the accumulated ammonium ion, carbamoyl phosphate synthetase I (CPS I) and ornithine transcarbamoylase (OTC) were used, which catalyze the first and second steps of the urea cycle in the liver. To examine the effects of overexpressed CPS I and OTC genes on the concentration of the ammonium ion in culture media, the two genes were introduced into Chinese hamster ovary (CHO) dhfr-cells. The CPS I expressing cell lines (CPS I-CHO) and both CPS I and OTC expressing cell lines (CPS I/OTC-CHO) were confirmed at the mRNA level and analyzed in terms of the cell growth and the accumulation of ammonium ion in culture media. The accumulation of ammonium ion was ≃25-33% less in CPS I/OTC-CHO than in either CPS I-CHO or the vector-control cell lines. Interestingly however, the cell growth was ≃15-30% faster in both CPS I-CHO and CPS I/OTC-CHO than in the control cell lines. Forced expression of urea cycle enzymes in the CHO cells revealed that both the expression of CPS I and OTC can reduce the accumulation of ammonium ion in the culture media. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)129-140
Number of pages12
JournalJournal of Biotechnology
Issue number2-3
Publication statusPublished - 2000 Aug 25



  • Ammonium ion
  • Carbamoyl phosphate synthetase
  • CHO cells
  • Ornithine transcarbamoylase
  • Urea cycle

ASJC Scopus subject areas

  • Biotechnology

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