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FBA-based simulator of Saccharomyces cerevisiae fed-batch cultures involving an internal unbalanced metabolite

par Plaza Dorado, José ;Bogaerts, Philippe
Référence IFAC-PapersOnLine, 52, 26, page (169-174)
Publication Publié, 2019-12-01

Article révisé par les pairs

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Résumé :

A dynamic macroscopic simulator based on Flux Balance Analysis (FBA) is proposed to predict the dynamics of biomass growth, substrate consumption (glucose and ammonium) and ethanol production in S. cerevisiae fed-batch cultures. It is based on a metabolic network containing the main metabolism of the yeast, an objective cost function aiming at maximizing the biomass growth, different inequalities corresponding to some biological assumptions such as glucose overflow metabolism and inequalities which link the fluxes to models of substrate uptake rates. Since it was not possible to accurately correlate the input fluxes with only the extracellular species concentration, a new variable is introduced in the uptake rate models using the information at intracellular level. We first determine the dynamics corresponding to the intracellular metabolite, namely alpha-ketoglutarate, and, in a second part, this new information is used for modelling the input flux rates. Secondly, all the information is integrated in a set of mass balances for building a simulator based only on the initial conditions of each species and the feeding rate. It is validated with direct and cross-validation. This model allows, on the one hand, reproducing the dynamics of extracellular species and, on the other hand, describing the accumulation of alpha-ketoglutarate.