title: Arginine biosynthesis in Escherichia coli: experimental perturbation and mathematical modeling.
abstract: A basic challenge in cell biology is to understand how interconnected metabolic pathways are regulated to provide the adequate cellular outcome when changing levels of metabolites and enzyme expression. In Escherichia coli, the arginine and pyrimidine biosynthetic pathways are connected through a common metabolite provided by a single enzyme. The different elements of the arginine biosynthetic system of Escherichia coli, including the connection with pyrimidine biosynthesis, and the principal regulatory mechanisms operating at genetic and enzymatic levels were integrated in a mathematical model using a molecular kinetic approach combined with a modular description of the system. The model was then used to simulate a set of perturbed conditions as follows: genetic derepression, feedback resistance of the first enzymatic step, and low constitutive synthesis of the intermediate carbamyl phosphate. In all cases, an excellent quantitative agreement between simulations and experimental results was found. The model was used to gain further insight into the function of the system, including the synergy between the different regulations. The outcome of combinations of perturbations on cellular arginine concentration was predicted accurately, establishing the model as a powerful tool for the design of arginine-overproducing strains.
authors.affiliation: Laboratory of Microbiology and Genetics, Vrije Universiteit Brussel, Pleinlaan 2, Brussels, Belgium.
authors.forename: Marina
authors.initials: M
authors.lastname: Caldara
authors.forename: Geneviève
authors.initials: G
authors.lastname: Dupont
authors.forename: Frédéric
authors.initials: F
authors.lastname: Leroy
authors.forename: Albert
authors.initials: A
authors.lastname: Goldbeter
authors.forename: Luc
authors.initials: L
authors.lastname: De Vuyst
authors.forename: Raymond
authors.initials: R
authors.lastname: Cunin
mesh_terms: D001120:Arginine / Q000096:biosynthesis*; D004926:Escherichia coli / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D001120:Arginine