title: Computational prediction of essential metabolic genes using constraint-based approaches.
abstract: In this chapter, we describe the application of constraint-based modeling to predict the impact of gene deletions on a metabolic phenotype. The metabolic reactions taking place inside cells form large networks, which have been reconstructed at a genome-scale for several organisms at increasing levels of detail. By integrating mathematical modeling techniques with biochemical principles, constraint-based approaches enable predictions of metabolite fluxes and growth under specific environmental conditions or for genetically modified microorganisms. Similar to the experimental knockout of a gene, predicting the essentiality of a metabolic gene for a phenotype further allows to generate hypotheses on its biological function and design of genetic engineering strategies for biotechnological applications. Here, we summarize the principles of constraint-based approaches and provide a detailed description of the procedure to predict the essentiality of metabolic genes with respect to a specific metabolic function. We exemplify the approach by predicting the essentiality of reactions in the citric acid cycle for the production of glucose from fatty acids.
authors: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas (CSIC), Profesor Albareda 1, 18008, Granada, Spain, georgbasler@yahoo.de.
authors: Georg
authors: G
authors: Basler
mesh_terms: D002952:Citric Acid Cycle / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D020043:Genes, Essential; D064688:Metabolic Flux Analysis; D008660:Metabolism / Q000235:genetics*