In silica Design of Metabolic Pathway of Yet for Bio-ProductionofEnvironmental-Conscious Chemical Products

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The objective of this study is to establish a genome-scale model for prediction of change of metabolic pathways and design methodology for production of environmental-conscious chemicals in yeast. Seocharomyces cerevisiae was used as a model microorganism for this objective. A novel method to predict in silico effect of change of gene expression level on change of metabolic fluxes in the cells was developed.Genome scale model was constructed by integration of genome information as a set of stoichiometric form of metabolic reactions. This model does not involve any kinetic information and this enables us to minimize the load of the model construction and parameter estimation in the model. Targeted chemicals for environmental-conscious materials are selected in the metabolic pathways of central carbon metabolism around glycolysis, TCA cycle, biosynthesis of amino acids. Modification of metabolic pathways based on the gene knock out was designed with the developed system.An experimental validation and evaluation system for metabolic flux change was also developed. Precise metabolic flux evaluation system for central carbon metabolism of yeast was established.130-labeled chemical compound was consumed by cells experimentally and enrichment of labeled carbon was analyzed by gas chromatography mass spectrometry (GC-MS). For achieving the objective, a central carbon metabolism model was constructed by taking into amount of atom mapping.The systems developed in this study were well developed and applied for production of succinic acid in yeast.