2.2. Influence of Transcription sellekchem factors on Gene Expression To determine the κi coefficients for the model, NCA was applied with three data sets. In addition, transcription factor activities could

be determined as well and compared with biological knowledge on the system. The model is similar to the previous one [3]: 32 transcriptional units are used and three transcription factors are considered (Crp, ArcA, and FruR). Although other transcription factors such as Fnr, SoxS or PdhR influence some of the genes, they are not Inhibitors,research,lifescience,medical considered explicitly here, since they are not involved in sensing metabolic fluxes in glycolysis. The number of time points is 35 (16 from growth on glucose and lactose [12], 18 from the glucose pulse experiment in this study, and 1 from growth on acetate [13]). Although strains that are used

in the cited studies are different, a comparison of the growth behavior for the strains used in [12,14] reveals consistency with respect to the growth rate. Experiments in this study Inhibitors,research,lifescience,medical were performed with the same strain as in [14]. Since from [13] only one data point was taken into account, Inhibitors,research,lifescience,medical the entire data set can be regarded as consitent. As described above, elements of the coupling matrix K and transcription factor activities TF are determined with NCA. Figure 3 shows the results for strain LJ110 after a glucose pulse. In a continuous culture, E. coli grows under glucose limited conditions. At time point zero, glucose was pulsed and the dynamics of the extracellular components and biomass was followed. Plot A shows the time course for glucose (diamonds) and acetate (squares). Three phases can be seen and are marked with vertical lines: After 10 h, glucose is depleted; at time point 15 h E. Inhibitors,research,lifescience,medical coli switches to growth on acetate, and after 20 h acetate is depleted. Plots B/C shows the Inhibitors,research,lifescience,medical corresponding activities of the transcription factors Crp and FruR, respectively. sellckchem During growth on glucose, Crp activity is low and after depletion of glucose, Crp activity becomes more and more active. In contrast, FruR activity

is high during growth on glucose (since inducer fructose-1,6-bisphosphate is expected to be high in this phase [15]), and only after shift to acetate uptake, FruR activity becomes lower as expected from other experiments [16]. Figure 3 Left (plot A): experimental data for glucose (diamonds) and acetate (squares); Drug_discovery middle (plot B) NCA results: Crp transcription factor activity; right (plot C) NCA results: FruR transcription factor activity. Circles indicate the sampling time points for … The elements of the coupling matrix K that were needed for the core model of the glycolysis are summarized in Table 2. Values are given for the genes pfkA, eno, gap, and pykF. See Appendix for a complete plot with all entries of K. Table 2 Entries κi of the coupling matrix K. In further calculations the two values for eno and gap (κ2) are taken as representatives for the lumped glyoclytic reaction rgly.