Yeo2020 - Genome-scale model of CHO cells

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The iCHO2291 model was reconstructed by updating the previously published iCHO1766 model in a 6-step procedure: 1) identification and removal of duplicate metabolites and reactions, 2) replacement of lumped reactions into detailed steps and removal of biochemically inconsistent reactions, 3) update of GPR based on latest genome annotations (as on Nov 1, 2018), 4) correction of GPR and reaction compartment assignment based on subcellular localization, 5) inclusion of new reactions based on new genome annotations, and 6) metabolic gap identification and resolution.
Related Publication
  • Enzyme capacity-based genome scale modelling of CHO cells.
  • Yeo HC, Hong J, Meiyappan Lakshmanan, Lee DY
  • Metabolic engineering , 7/ 2020 , Volume 60 , pages: 138-147 , PubMed ID: 32330653
  • Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, 138668, Singapore; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585, Singapore.
  • Chinese hamster ovary (CHO) cells are most prevalently used for producing recombinant therapeutics in biomanufacturing. Recently, more rational and systems approaches have been increasingly exploited to identify key metabolic bottlenecks and engineering targets for cell line engineering and process development based on the CHO genome-scale metabolic model which mechanistically characterizes cell culture behaviours. However, it is still challenging to quantify plausible intracellular fluxes and discern metabolic pathway usages considering various clonal traits and bioprocessing conditions. Thus, we newly incorporated enzyme kinetic information into the updated CHO genome-scale model (iCHO2291) and added enzyme capacity constraints within the flux balance analysis framework (ecFBA) to significantly reduce the flux variability in biologically meaningful manner, as such improving the accuracy of intracellular flux prediction. Interestingly, ecFBA could capture the overflow metabolism under the glucose excess condition where the usage of oxidative phosphorylation is limited by the enzyme capacity. In addition, its applicability was successfully demonstrated via a case study where the clone- and media-specific lactate metabolism was deciphered, suggesting that the lactate-pyruvate cycling could be beneficial for CHO cells to efficiently utilize the mitochondrial redox capacity. In summary, iCHO2296 with ecFBA can be used to confidently elucidate cell cultures and effectively identify key engineering targets, thus guiding bioprocess optimization and cell engineering efforts as a part of digital twin model for advanced biomanufacturing in future.
Meiyappan Lakshmanan, Rahuman Sheriff

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iCHO2291.xml Genome-scale model of CHO cells (iCHO2291) 14.00 MB Preview | Download

  • Model originally submitted by : Meiyappan Lakshmanan
  • Submitted: May 28, 2020 1:13:40 PM
  • Last Modified: May 28, 2020 1:13:40 PM
  • Version: 6 public model Download this version
    • Submitted on: May 28, 2020 1:13:40 PM
    • Submitted by: Rahuman Sheriff
    • With comment: Edited model metadata online.
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