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Modeling and optimization of the production of lipids by oleaginous yeasts

Abstract : This PhD thesis aims at optimizing lipid accumulation by oleaginous yeast, and most particularly by the yeast Yarrowia lipolytica from glucose. This optimization is addressed from a mathemantical point of view based on automatic control laws, where model-based control strategies are proposed. The bibliographic review compiles and evaluates previous works to identify the different existing methodologies to attain the optimization, which is divided in three main axes: modeling, control strategies, and monitoring. In this context, five different models are proposed to describe lipid accumulation. The first model is based on Monod and inhibition kinetics (unstructured), and the second on the Droop quota model (quota) previously used for microalgae. The last three are dynamic metabolic models that combine kinetics with metabolic models based on the stoichiometry of metabolism. These three models used a reduced metabolic network decomposed into elementary flux modes. The five models were successfully calibrated and validated with different experimental data. Nonetheless, the dynamic metabolic models presented highlighting features such as the description of metabolic shifts. Two approaches of multi-objective control strategies aiming at maximizing lipid productivity and lipid content fraction were proposed. In the first, the two objectives were weighted by static calculation of Pareto fronts, and integrated to the control strategy by dynamic optimization algorithms with a dynamic metabolic model. The second strategy used a constant weighed objective function solved by piecewise linear functions by integrating the quota model. The simulation results of the optimization attained lipid contents between 0.21 – 0.26 gLIP.gX-1 and productivities between 0.78 – 1.02 g.(L-h)-1 shortening the culture time to 20 h. Soft-sensors were developed by correlating on-line measurements (i.e. pO2 and the added base for pH) through support vector machines in order to overcome the lack of measurements. The perspective is to experimentally validate the control strategies.
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Submitted on : Thursday, February 22, 2018 - 5:00:08 PM
Last modification on : Tuesday, March 17, 2020 - 3:17:55 AM
Long-term archiving on: : Wednesday, May 23, 2018 - 2:36:27 PM


Version validated by the jury (STAR)


  • HAL Id : tel-01715462, version 1


Carlos Eduardo Robles Rodriguez. Modeling and optimization of the production of lipids by oleaginous yeasts. Microbiology and Parasitology. INSA de Toulouse, 2016. English. ⟨NNT : 2016ISAT0044⟩. ⟨tel-01715462⟩



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