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Metabolic modeling under non-balanced growth. Application to microalgae for biofuels production

Caroline Baroukh 1, 2
2 BIOCORE - Biological control of artificial ecosystems
LOV - Laboratoire d'océanographie de Villefranche, CRISAM - Inria Sophia Antipolis - Méditerranée , INRA - Institut National de la Recherche Agronomique
Abstract : Metabolic modeling is a powerful tool to understand, predict and optimize bioprocesses, particularly when they imply intracellular molecules of interest. Unfortunately, the use of metabolic models for time varying metabolic fluxes is hampered by the lack of experimental data required to define and calibrate the kinetic reaction rates of the metabolic pathways. For this reason, metabolic models are often used under the balanced growth hypothesis. However, for some processes such as the photoautotrophic metabolism of microalgae, the balanced-growth assumption appears to be unreasonable because of the synchronization of their circadian cycle on the daily light. Yet, understanding microalgae metabolism is necessary to optimize the production yield of bioprocesses based on this microorganism, as for example production of third-generation of biofuels. In this PhD thesis, DRUM, a new dynamic metabolic modeling framework that handles the non-balanced growth condition and hence accumulation of intracellular metabolites was developed. The first stage of the approach consists in splitting the metabolic network into sub-networks describing reactions which are spatially and functionally close, and which are assumed to satisfy balanced growth condition. The left metabolites interconnecting the sub-networks behave dynamically. Then, thanks to Elementary Flux Mode analysis, each sub-network is reduced to macroscopic reactions, for which simple kinetics are assumed. Finally, an Ordinary Differential Equation system is obtained to describe substrate consumption, biomass production, products excretion and accumulation of some internal metabolites. DRUM was applied to the accumulation of lipids and carbohydrates of the microalgae Tisochrysis lutea under day/night cycles in normal and nitrogen starvation conditions. The resulting model describes accurately experimental data. It efficiently predicts the accumulation and consumption of lipids and carbohydrates. DRUM was also applied to the microalgae Chlorella sorokiniana in dark heterotrophic growth, showing that the balanced-growth assumption was valid in this case.
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Submitted on : Thursday, January 22, 2015 - 10:29:32 PM
Last modification on : Saturday, June 26, 2021 - 3:14:18 AM
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  • HAL Id : tel-01108542, version 1


Caroline Baroukh. Metabolic modeling under non-balanced growth. Application to microalgae for biofuels production. Automatic Control Engineering. Université Montpellier 2, 2014. English. ⟨tel-01108542⟩



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