Microbial Gene Essentiality: Protocols and Bioinformatics

Volume 416 of the series Methods in Molecular Biology™ pp 409-431

Design and Application of Genome-Scale Reconstructed Metabolic Models

  • Isabel RochaAffiliated withCentro de Engenharia Biológica, Universidade do Minho
  • , Jochen FörsterAffiliated withFluxome Sciences A/S
  • , Jens NielsenAffiliated withCenter for Microbial Biotechnology Biocentrum, Technical University of Denmark

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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; identification of the reactions from the annotated genome sequence and available literature; determination of the reaction stoichiometry; definition of compartmentation and assignment of localization; determination of the biomass composition; measurement, calculation, or fitting of energy requirements; and definition 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 flux 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.

Key Words

computer simulation fluxome analysis genome annotation genome-scale reconstruction metabolic engineering metabolic flux analysis metabolic models metabolic networks