2007
DOI: 10.1021/bp060089y
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Dynamic Metabolic Modeling for a MAB Bioprocess

Abstract: Production of monoclonal antibodies (MAb) for diagnostic or therapeutic applications has become an important task in the pharmaceutical industry. The efficiency of high-density reactor systems can be potentially increased by model-based design and control strategies. Therefore, a reliable kinetic model for cell metabolism is required. A systematic procedure based on metabolic modeling is used to model nutrient uptake and key product formation in a MAb bioprocess during both the growth and post-growth phases. T… Show more

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Cited by 41 publications
(52 citation statements)
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“…18 The CHO metabolic network has been adapted from a Hybridoma metabolic model developed by us. 19 The metabolic network includes the main pathways of glycolysis, the TCA cycle, energy related amino acid metabolism, and production of biomass and MAb. It consists of 30 metabolites involved in 34 bioreactions.…”
Section: Metabolic Flux Analysismentioning
confidence: 99%
See 1 more Smart Citation
“…18 The CHO metabolic network has been adapted from a Hybridoma metabolic model developed by us. 19 The metabolic network includes the main pathways of glycolysis, the TCA cycle, energy related amino acid metabolism, and production of biomass and MAb. It consists of 30 metabolites involved in 34 bioreactions.…”
Section: Metabolic Flux Analysismentioning
confidence: 99%
“…The values of R are obtained for each phase separately. 10,19 The transition from one phase to the next corresponds to cessation of growth and the cell's consequent metabolic adaptation to new conditions. Then, the intracellular fluxes in each phase are calculated using a steady-state mass balance equation and determining the conversion/production rate, R m , of each metabolite from stoichiometric relationships.…”
Section: Metabolic Flux Analysismentioning
confidence: 99%
“…To reduce the size and complexity of the system, significant intracellular fluxes were identified using MFA, and distinct characteristics were assigned to the different phases of the culture. The model is capable of predicting glucose and glutamine and the key amino acid concentrations as well as product formation [122]. This model was taken by Baughman et al [123] to illustrate an optimization-based technique for the estimation of kinetic parameter values in dynamic models of cell metabolism, based on algebraic approximations of continuous differential equations.…”
Section: Dynamic Modelsmentioning
confidence: 99%
“…Previous studies have used metabolic flux analysis to construct mathematical models of mammalian cell culture processes by correlating cell growth to metabolic activities triggered by extracellular nutrient availability (Bonarius et al, 1996;Follstad et al, 1999;Gao et al, 2007). As nutrients are depleted and metabolic activity slows down, growth stops and apoptosis is triggered.…”
Section: Motivationmentioning
confidence: 99%