growth rate) with a newly designed strain. Estimation of lumped kinetic parameters. The additional data allow an improved estimation of kinetic parameters. Prediction of the steady behavior of the intracellular metabolites over a broad range of the growth rate. The approach is summarized in Figure 1. Figure 1 Outline on the approach. Array data, input/output data and time course data are used to set up and analyze #Tivantinib in vitro randurls[1|1|,|CHEM1|]# the model. After parameter fitting,

the comparison and validation of the model are performed. 1.1. Background Figure 2 shows the core reactions of glycolysis in E. coli. As can be seen, the regulatory structure for growth on carbohydrates Inhibitors,research,lifescience,medical can be subdivided into genetic control via transcription factor FruR and metabolic control

via feedforward and feedback loops. Figure 2 Glycolytic mode of central metabolism of Inhibitors,research,lifescience,medical E. coli including important regulations. Glucose is mainly taken up by PtsG, but other unspecific transport systems are also available (non-PTS). Shown are transcriptional control via FruR and allosteric control. … Glucose represents the preferred carbohydrate of Escherichia coli K-12 and is taken up mainly by the glucose transporter PtsG. Several other carbohydrates feeding into the upper part of glycolysis Inhibitors,research,lifescience,medical also allow for fast growth. Organic acids such as acetate which demand an active gluconeogenesis can also be used as growth substrates but generally the growth rates on these substrates are comparatively slow. Uptake of many glycolytic substrates is catalyzed by the PTS. This system uses PEP as phosphate donor. The phosphoryl group from PEP is firstly transferred to EI in an autocatalytic reaction. EI transfers the phosphorylgroup to HPr and HPr is able to phosphorylate a number of substrate specific Inhibitors,research,lifescience,medical EIIs that catalyse uptake and phosphorylation of their respective substrates [5]. In the case of glucose the PTS represents the most important uptake system but uptake of glucose is also possible by a number of non-PTS systems such as GalP and MglABC. Metabolism

Inhibitors,research,lifescience,medical of carbohydrates is tightly controlled. Typically, the genes encoding carbohydrate uptake systems are controlled on the genetic level. In most cases induction is exerted by the specific substrate of the uptake system e.g., lactose or arabinose. In addition, many of these systems are subject to global control by cAMP∙Crp [5]. The activity of the transcription factor cAMP∙Crp is controlled on many levels. Crp concentrations in a cell either can vary in response to changing growth conditions. But the most important factor determining cAMP∙Crp activity is the intracellular cAMP concentration. This is in turn determined by the phosphorylation state of the PTS protein EIIAGlc. During growth on glucose or other carbon sources allowing fast growth EIIAGlc is present mainly in its unphosphorylated form while during growth with poor carbon sources EIIAGlc is present in its phosphorylated form [1,6].