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Evolutionary approaches for strain optimization using dynamic models under a metabolic engineering perspective

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Resumo:One of the purposes of Systems Biology is the quantitative modeling of biochemical networks. In this effort, the use of dynamical mathematical models provides for powerful tools in the prediction of the phenotypical behavior of microorganisms under distinct environmental conditions or subject to genetic modifications. The purpose of the present study is to explore a computational environment where dynamical models are used to support simulation and optimization tasks. These will be used to study the effects of two distinct types of modifications over metabolic models: deleting a few reactions (knockouts) and changing the values of reaction kinetic parameters. In the former case, we aim to reach an optimal knockout set, under a defined objective function. In the latter, the same objective function is used, but the aim is to optimize the values of certain enzymatic kinetic coefficients. In both cases, we seek for the best model modifications that might lead to a desired impact on the concentration of chemical species in a metabolic pathway. This concept was tested by trying to maximize the production of dihydroxyacetone phosphate, using Evolutionary Computation approaches. As a case study, the central carbon metabolism of Escherichia coli is considered. A dynamical model based on ordinary differential equations is used to perform the simulations. The results validate the main features of the approach.
Autores principais:Evangelista, Pedro
Outros Autores:Rocha, I.; Ferreira, Eugénio C.; Rocha, Miguel
Ano:2009
País:Portugal
Tipo de documento:comunicação em conferência
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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