Modeling and optimization of a multi-product biosynthesis factory for multiple objectives |
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| Authors: | Fook Choon Lee Gade Pandu Rangaiah Dong-Yup Lee |
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| Institution: | 1. Department of Chemical & Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore;2. School of Chemical and Life Sciences, Singapore Polytechnic, 500 Dover Road, Singapore 139651, Singapore;3. Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Centros, Singapore 138668, Singapore;1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore 117599, Singapore;2. NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore;3. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore;1. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore;2. Division of Heat and Power Technology, Department of Energy and Environment, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden;1. Bioprocessing Technology Institute, A*STAR (Agency for Science, Technology and Research), 20 Biopolis Way, #06-01 Centros, 138668 Singapore, Singapore;2. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore;1. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore;2. NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore;3. Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore;4. Sangon Biotech (Shanghai) Co., Ltd., 698 Xiangmin Road, SongJiang District, Shanghai 201611, China |
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| Abstract: | Genetic algorithms and optimization in general, enable us to probe deeper into the metabolic pathway recipe for multi-product biosynthesis. An augmented model for optimizing serine and tryptophan flux ratios simultaneously in Escherichia coli, was developed by linking the dynamic tryptophan operon model and aromatic amino acid-tryptophan biosynthesis pathways to the central carbon metabolism model. Six new kinetic parameters of the augmented model were estimated with considerations of available experimental data and other published works. Major differences between calculated and reference concentrations and fluxes were explained. Sensitivities and underlying competition among fluxes for carbon sources were consistent with intuitive expectations based on metabolic network and previous results. Biosynthesis rates of serine and tryptophan were simultaneously maximized using the augmented model via concurrent gene knockout and manipulation. The optimization results were obtained using the elitist non-dominant sorting genetic algorithm (NSGA-II) supported by pattern recognition heuristics. A range of Pareto-optimal enzyme activities regulating the amino acids biosynthesis was successfully obtained and elucidated wherever possible vis-à-vis fermentation work based on recombinant DNA technology. The predicted potential improvements in various metabolic pathway recipes using the multi-objective optimization strategy were highlighted and discussed in detail. |
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