Macrokinetic model for methylotrophic Pichia pastoris based on stoichiometric balance

Research output: Contribution to journalArticleResearchpeer review

Authors

  • H. T. Ren
  • J. Q. Yuan
  • K. H. Bellgardt

Research Organisations

External Research Organisations

  • Shanghai Jiaotong University
  • East China University of Science and Technology
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Details

Original languageEnglish
Pages (from-to)53-68
Number of pages16
JournalJournal of biotechnology
Volume106
Issue number1
Early online date23 Oct 2003
Publication statusPublished - 5 Dec 2003

Abstract

A macrokinetic model for Pichia pastoris expressing recombinant human serum albumin is proposed. The model describes the balances of some key metabolites, ATP and NADH, during glycerol and methanol metabolism. In the glycerol growth phase, the metabolic pathways mainly include phosphorylation, glycolysis, tricarboxylic acid cycle, and respiratory chain. In the methanol growth phase, methanol is oxidized to formaldehyde at first. Then, while a part of formaldehyde is oxidized to formate, the rest is condensed with xylulose-5-monophosphate to form glyceraldehyde-3-phosphate, and further assimilated to form cell constituents. The metabolic pathways following glyceraldehyde-3-phosphate were assumed to be similar to those in the glycerol growth phase. Based on the model, the macrokinetic bioreaction rates such as the specific substrate consumption rate, the specific growth rate, the specific acetyl-CoA formation rate as well as the specific oxygen uptake rate are obtained. The specific substrate consumption rate and the specific growth rate are then coupled into a bioreactor model such that the relationship between substrate feeding rates and the main state variables, i.e., the medium volume, the concentrations of the biomass, the substrate, and the product, is set up. Experimental results demonstrate that the model can describe the cell growth and the protein production with reasonable accuracy.

Keywords

    Metabolic pathways, Pichia pastoris, Recombinant human serum albumin, Stoichiometric model

ASJC Scopus subject areas

Cite this

Macrokinetic model for methylotrophic Pichia pastoris based on stoichiometric balance. / Ren, H. T.; Yuan, J. Q.; Bellgardt, K. H.
In: Journal of biotechnology, Vol. 106, No. 1, 05.12.2003, p. 53-68.

Research output: Contribution to journalArticleResearchpeer review

Ren HT, Yuan JQ, Bellgardt KH. Macrokinetic model for methylotrophic Pichia pastoris based on stoichiometric balance. Journal of biotechnology. 2003 Dec 5;106(1):53-68. Epub 2003 Oct 23. doi: 10.1016/j.jbiotec.2003.08.003
Ren, H. T. ; Yuan, J. Q. ; Bellgardt, K. H. / Macrokinetic model for methylotrophic Pichia pastoris based on stoichiometric balance. In: Journal of biotechnology. 2003 ; Vol. 106, No. 1. pp. 53-68.
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