Application of metabolic engineering principles to the rational design of microbial production processes crucially depends on the ability to describe quantitatively the systemic behavior of the central carbon metabolism to redirect carbon fluxes to the product-forming pathways. Despite the importance for several production processes, development of an essential dynamic model for central carbon metabolism of Escherichia coli has been severely hampered by the current lack of kinetic information on the dynamics of the metabolic reactions. Here we present the design and experimental validation of such a dynamic model, which, for the first time, links the sugar transport system (i.
View Article and Find Full Text PDFThe application of metabolic engineering principles to the rational design of microbial production processes crucially depends on the ability to make quantitative descriptions of the systemic ability of the central carbon metabolism to redirect fluxes to the product-forming pathways. The aim of this work was to further our understanding of the steps controlling the biotransformation of trimethylammonium compounds into L-carnitine by Escherichia coli. Despite the importance of L-carnitine production processes, development of a model of the central carbon metabolism linked to the secondary carnitine metabolism of E.
View Article and Find Full Text PDFThis paper examines the validity of the linlog approach, which was recently developed in our laboratory, by comparison of two different kinetic models for the metabolic network of Escherichia coli. The first model is a complete mechanistic model; the second is an approximative model in which linlog kinetics are applied. The parameters of the linlog model (elasticities) are derived from the mechanistic model.
View Article and Find Full Text PDFThe presumably high potential of a holistic design approach for complex biochemical reaction networks is exemplified here for the network of tryptophan biosynthesis from glucose, a system whose components have been investigated thoroughly before. A dynamic model that combines the behavior of the trp operon gene expression with the metabolic network of central carbon metabolism and tryptophan biosynthesis is investigated. This model is analyzed in terms of metabolic fluxes, metabolic control, and nonlinear optimization.
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