A dynamic metabolic flux balance based model of fed‐batch fermentation of bordetella pertussis |
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Authors: | Hector Budman Nilesh Patel Melih Tamer Walid Al‐Gherwi |
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Affiliation: | 1. Dept. of Chemical Engineering, University of Waterloo, , Waterloo, ON, Canada;2. Manufacturing Technology, Sanofi Pasteur Canada, , ON, Canada |
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Abstract: | A mathematical model based on a dynamic metabolic flux balance (DMFB) is developed for a process of fed‐batch fermentation of Bordetella pertussis. The model is based on the maximization of growth rate at each time interval subject to stoichiometric constraints. The model is calibrated and verified with experimental data obtained in two different bioreactor experimental systems. It was found that the model calibration was mostly sensitive to the consumption or production rates of tyrosine and, for high supplementation rates, to the consumption rate of glutamate. Following this calibration the model correctly predicts biomass and by‐products concentrations for different supplementation rates. Comparisons of model predictions to oxygen uptake and carbon emission rates measurements indicate that the TCA cycle is fully functional. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 520–531, 2013 |
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Keywords: | dynamic metabolic flux model Bordetella pertussis |
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