Design and Application of Genome-Scale Reconstructed Metabolic Models

In this chapter, the process for the reconstruction of genome-scale metabolic networks is described, and some of the main applications of such models are illustrated. The reconstruction process can be viewed as an iterative process where information obtained from several sources is combined to construct a preliminary set of reactions and constraints. This involves steps such as genome annotation; identifi cation of the reactions from the annotated genome sequence and available literature; determination of the reaction stoichiometry; defi nition of compartmentation and assignment of localization; determination of the biomass composition; measurement, calculation, or fi tting of energy requirements; and defi nition of additional constraints. The reaction and constraint sets, after debugging, may be integrated into a stoichiometric model that can be used for simulation using tools such as Flux Balance Analysis (Section 3.8). From the fl ux distributions obtained, physiologic parameters such as growth yields or minimal medium components can be calculated, and their distance from similar experimental data provides a basis from where the model may need to be improved.