In Silico Analysis of the Escherichia Coli Metabolic Genotype and the Construction of Selected Isogenic Strains
Bernhard O. Palsson
University of California-San Diego

Small genome sequencing and annotation are leading to the definition of metabolic genotypes in an increasing number of organisms. We show how in silico metabolic genotypes are formulated based on genomic, biochemical, and strain-specific data.  Such metabolic genotypes have been formulated for E. coli, H. influenzae, and H. pylori.  The in silico models are based on the philosophy of using applicable physico-chemical (such as stoichiometric structure) and capacity (maximum fluxes) constraints on the integrated functioning of the metabolic networks.  Given these constraints, optimal phenotypes can be computed and compared to experimental data.  They are found on the edge of the allowable solution spaces ö a space that basically represents the reaction norm of the defined genotype ö where the governing constraint on cellular functions can be identified.  For E. coli, this process leads to quantitative prediction of growth and metabolic by-product secretion data in batch, fed-batch, and continuous cultures, and to the accurate prediction of the metabolic capabilities of 73 of 80 mutants examined.  Furthermore, we present mathematical methods that allow for the analysis, interpretation, prediction, and engineering of the metabolic genotype-phenotype relationship, and for the interpretation of expression array data.

Key refs:
J.S. Edwards and B.O. Palsson,  "The Escherichia coli MG1655 in silico metabolic genotype; Its definition, characteristics, and capabilities," Proc. Natl Acad Sci (USA), 97: 5528-5523 (2000).

J.S. Edwards, R.U. Ibarra, and B.O. Palsson, "In silico predictions of Escherichi coli metabolic capabilities are consistent with experimental data," Nature Biotechnology,  19:125, 2001

Return to Table of Contents