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CHOmpact: a reduced metabolic model of Chinese hamster ovary cells with enhanced interpretability

View ORCID ProfileIoscani Jiménez del Val, Sarantos Kyriakopoulos, View ORCID ProfileSimone Albrecht, View ORCID ProfileHenning Stockmann, View ORCID ProfilePauline M Rudd, View ORCID ProfileKaren M Polizzi, View ORCID ProfileCleo Kontoravdi
doi: https://doi.org/10.1101/2021.07.19.452953
Ioscani Jiménez del Val
1School of Chemical & Bioprocess Engineering, University College Dublin D04 V1W8, Ireland
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  • For correspondence: ioscani.jimenezdelval@ucd.ie
Sarantos Kyriakopoulos
2MS&T, BioMarin Manufacturing Ireland, Cork P43 R298, Ireland
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Simone Albrecht
3NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Dublin A94 X099, Ireland
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Henning Stockmann
3NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Dublin A94 X099, Ireland
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Pauline M Rudd
3NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Dublin A94 X099, Ireland
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Karen M Polizzi
4Department of Chemical Engineering, Imperial College London SW7 2AZ, United Kingdom
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Cleo Kontoravdi
4Department of Chemical Engineering, Imperial College London SW7 2AZ, United Kingdom
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Abstract

Metabolic modelling has emerged as a key tool for the characterisation of biopharmaceutical cell culture processes. Metabolic models have also been instrumental in identifying genetic engineering targets and developing feeding strategies that optimise the growth and productivity of Chinese hamster ovary (CHO) cells. Despite their success, metabolic models of CHO cells still present considerable challenges. Genome scale metabolic models (GeMs) of CHO cells are very large (>6000 reactions) and are, therefore, difficult to constrain to yield physiologically consistent flux distributions. The large scale of GeMs also makes interpretation of their outputs difficult. To address these challenges, we have developed CHOmpact, a reduced metabolic network that encompasses 101 metabolites linked through 144 reactions. Our compact reaction network allows us to deploy multi-objective optimisation and ensure that the computed flux distributions are physiologically consistent. Furthermore, our CHOmpact model delivers enhanced interpretability of simulation results and has allowed us to identify the mechanisms governing shifts in the anaplerotic consumption of asparagine and glutamate as well as an important mechanism of ammonia detoxification within mitochondria. CHOmpact, thus, addresses key challenges of large-scale metabolic models and, with further development, will serve as a platform to develop dynamic metabolic models for the control and optimisation of biopharmaceutical cell culture processes.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 20, 2021.
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CHOmpact: a reduced metabolic model of Chinese hamster ovary cells with enhanced interpretability
Ioscani Jiménez del Val, Sarantos Kyriakopoulos, Simone Albrecht, Henning Stockmann, Pauline M Rudd, Karen M Polizzi, Cleo Kontoravdi
bioRxiv 2021.07.19.452953; doi: https://doi.org/10.1101/2021.07.19.452953
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CHOmpact: a reduced metabolic model of Chinese hamster ovary cells with enhanced interpretability
Ioscani Jiménez del Val, Sarantos Kyriakopoulos, Simone Albrecht, Henning Stockmann, Pauline M Rudd, Karen M Polizzi, Cleo Kontoravdi
bioRxiv 2021.07.19.452953; doi: https://doi.org/10.1101/2021.07.19.452953

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