Affiliations: 1Institut für Biotechnologie 2, Forschungszentrum
Jülich GmbH, 52425 Jülich, Germany | 2Abteilung Theoretische Biologie, Botanisches
Institut, Universität Bonn, Kirschallee 1, 53115 Bonn, Germany | 3Abt. Simulationstechnik und Informatik, Institut
für Mechanik und Regelungstechnik, FB 11, Universität Siegen,
Paul-Bonatz-Str. 9-11, 57068 Siegen, Germany
Note: [] Corresponding author.
Abstract: The identification of metabolic regulation is a major concern in
metabolic engineering. Metabolic regulation phenomena depend on intracellular
compounds such as enzymes, metabolites and cofactors. A complete understanding
of metabolic regulation requires quantitative information about these compounds
under in vivo conditions. This quantitative knowledge in combination with the
known network of metabolic pathways allows the construction of mathematical
models that describe the dynamic changes in metabolite concentrations over
time. Rapid sampling combined with pulse experiments is a useful tool for the
identification of metabolic regulation owing to the transient data they
provide. Enzymatic tests in combination with ESI-LC-MS (Electrospray Ionization
Liquid Chromatographic Tandem Mass Spectrometry) and HPLC measurements have
been used to identify up to 30 metabolites and nucleotides from rapid sampling
experiments. A metabolic modeling tool (MMT) that is built on a relational
database was developed specifically for analysis of rapid sampling experiments.
The tool allows to construct complex pathway models with information stored in
the relational database. Parameter fitting and simulation algorithms for the
resulting system of Ordinary Differential Equations (ODEs) are part of MMT.
Additionally explicit sensitivity functions are calculated. The integration of
all necessary algorithms in one tool allows fast model analysis and comparison.
Complex models have been developed to describe the central metabolic pathways
of Escherichia coli during a glucose pulse experiment.
Keywords: metabolism modeling, rapid sampling, E. coli
