Figure 1.

Schematic representation of model construction. The genome can be classified as the first-level database. holding the potential functions of an organism. The transcriptome can be classified as the second-level database of functions describing the actual expression of genes, and the proteome can be classified as the third-level database of functions describing the actual expressed proteins. The metabolome (and fluxome) can be classified as the fourth-level database holding the complete collection of metabolites and reactions in which the metabolites participate. The metabolome, and to a lesser extent the proteome, determine the functionality of the cell [146]. In principle, all databases can be used as source of input for construction (or extension) of a genome-scale model (white arrows). In our study, information provided by the genome and the literature was used for model construction (black boxes). A minimal medium for growth was derived from the genome-scale model (upper gray box). The genome-scale model was simplified as descibed in the text, resulting in the 'putative model'. The measured specific metabolic rates and the corresponding measurement variances used in flux balance analysis (FBA) were calculated using Monte Carlo Simulation (MCS) with the measured experimental data and their standard deviation as input. The final model, verified by FBA, can be used for process development purposes (for example, optimization of growth medium, lower gray box). Subsequently, the model can be extended to the desired informative level using all available sources of information (light gray circle).