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Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model - Application to amino acid depletion in CHO cell culture.

Authors
  • Hagrot, Erika1
  • Oddsdóttir, Hildur Æsa2
  • Hosta, Joan Gonzalez1
  • Jacobsen, Elling W3
  • Chotteau, Véronique4
  • 1 Cell Technology Group, Department of Industrial Biotechnology/Bioprocess Design, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden; AdBIOPRO, Competence Centre for Advanced BioProduction by Continuous Processing, Sweden. , (Sweden)
  • 2 Department of Mathematics, Division of Optimization and Systems Theory, KTH Royal Institute of Technology, Stockholm, Sweden. , (Sweden)
  • 3 Department of Automatic Control, School of Electrical Engineering, KTH Royal Institute of Technology, Stockholm, Sweden. , (Sweden)
  • 4 Cell Technology Group, Department of Industrial Biotechnology/Bioprocess Design, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden; AdBIOPRO, Competence Centre for Advanced BioProduction by Continuous Processing, Sweden. Electronic address: [email protected] , (Sweden)
Type
Published Article
Journal
Journal of biotechnology
Publication Date
Oct 10, 2017
Volume
259
Pages
235–247
Identifiers
DOI: 10.1016/j.jbiotec.2017.05.026
PMID: 28689014
Source
Medline
Keywords
License
Unknown

Abstract

Mammalian cell lines are characterized by a complex and flexible metabolism. A single model that could describe the variations in metabolic behavior triggered by variations in the culture conditions would be a precious tool in bioprocess development. In this paper, we introduce an approach to generate a poly-pathway model and use it to simulate diverse metabolic states triggered in response to removal, reduction or doubling of amino acids in the culture medium of an antibody-producing CHO cell line. Macro-reactions were obtained from a metabolic network via elementary flux mode enumeration and the fluxes were modeled by kinetic equations with saturation and inhibition effects from external medium components. Importantly, one set of kinetic parameters was estimated using experimental data of the multiple metabolic states. A good fit between the model and the data was obtained for the majority of the metabolites and the experimentally observed flux variations. We find that the poly-pathway modeling approach is promising for the simulation of multiple metabolic states.

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