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Title: Optimization of Bioprocesses for multiple objectives
Keywords: modeling, optimization, Pareto, metabolic pathway recipe, concurrent gene knockout and manipulation
Issue Date: 30-Mar-2009
Source: LEE FOOK CHOON (2009-03-30). Optimization of Bioprocesses for multiple objectives. ScholarBank@NUS Repository.
Abstract: Modeling and optimization enable us to probe deeper into many processes including bioprocesses. In this study, two bioprocesses, penicillin V fermentation in an industrial biorector train and microbial cell factories Escherichia coli, were modeled and optimized for multiple objectives. Modeling of the penicillin V bioreactor train was done to set the stage for optimization studies for dual and triple objectives. There were two cases of bi-objective optimization: one involved simultaneous maximization of yield and penicillin concentration and the other one involved simultaneous maximization of yield and minimization of batch cycle time. Triple objective case involved the simultaneous maximization of yield, penicillin concentration and profit. Optimization of the central carbon metabolism of Escherichia coli was performed for maximizing the desired flux ratios, to find the optimal metabolic pathway recipe. In order to have a more detailed model, an augmented model linking the dynamic tryptophan operon model and aromatic amino acid-tryptophan biosynthesis pathways to the central carbon metabolism, was developed. Optimization was performed to simultaneously maximize the biosynthesis rates of serine and tryptophan using the augmented model via concurrent gene knockout and manipulation. The entire optimization results in this study were obtained using elitist non-dominated sorting genetic algorithm (NSGA-II). The results obtained were consistent with real data in an industrial setting for penicillin production and reported fermentation studies for Escherichia coli. Recommendations for future studies draw on the experience gained and likelihood of interesting insights.
Appears in Collections:Ph.D Theses (Open)

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