Transient responses of hybridoma metabolism to changes in the oxygen supply rate in continuous culture

W. M. Miller*, C. R. Wilke, H. W. Blanch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Oxygen is an important nutrient that may limit the productivity of commercial cell culture reactors. The transient responses of hybridoma growth and metabolism to step changes in the oxygen supply rate have been examined for dissolved oxygen concentrations (DO) ranging from 0.1% to 10% of air saturation in continuous culture. Metabolic quotients are reported for glucose, lactate, ammonia, oxygen, glutamine, alanine and other amino acids. A majority of the estimated ATP production was due to oxidative phosphorylation under all conditions tested. Decreases in the oxygen supply rate below the value required to maintain 0.5% DO caused the viable cell concentration to decrease. Glycolysis was enhanced at the lower oxygen concentrations, and after an initial decrease, the specific glutamine consumption rate was also higher. High residual glutamine concentrations occurred below 0.5% DO. Oxidation of other amino acids and production of serine were also inhibited. The cells subsequently adapted to low oxygen concentrations. The increase in cell concentration following the return to 10% DO was preceded by increased biosynthetic activity, as evidenced by transiently reduced yields of lactate from glucose, and alanine and ammonia from glutamine.

Original languageEnglish (US)
Pages (from-to)103-111
Number of pages9
JournalBioprocess Engineering
Issue number3
StatePublished - Sep 1 1988

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology


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