This title appears in the Scientific Report :
2001
Please use the identifier:
http://hdl.handle.net/2128/20235 in citations.
A pathway modeling tool for metabolic engineering
A pathway modeling tool for metabolic engineering
Identification of metabolic regulation is a key point in metabolic engineering. Metabolic regulation phenomena depend on intracellular compounds such as enzymes, metabolites, nucleotides and cofactors. Quantitative knowledge about these compounds in combination with the known network of metabolic pa...
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Personal Name(s): | Hurlebaus, Jochen (Corresponding author) |
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Contributing Institute: |
Biotechnologie 2; IBT-2 |
Imprint: |
Jülich
Forschungszentrum Jülich GmbH Zenralbibliothek, Verlag
2001
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Physical Description: |
XI, 184 p. |
Dissertation Note: |
Bonn, Univ., Diss., 2001 |
Document Type: |
Book Dissertation / PhD Thesis |
Research Program: |
Verfahrenstechnik zur mikrobiellen Gewinnung von Primärmetaboliten |
Series Title: |
Berichte des Forschungszentrums Jülich
3912 |
Subject (ZB): | |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Identification of metabolic regulation is a key point in metabolic engineering. Metabolic regulation phenomena depend on intracellular compounds such as enzymes, metabolites, nucleotides and cofactors. Quantitative knowledge about these compounds 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. The models are high-dimensional systems of ordinary, non-linear differential equations. To solve the problems of this approach (setup of the equations that describe the metabolic pathways in form of kinetic rate equations and the parameter identification of the System parameters), a variety of pathway modeling software has been developed over the last years. This work describes a Metabolic Modeling Tool (MMT) software for pathway analysis that is based on a relational database. It has been developed and applied to experimental data during this Ph.D. thesis . The software can be used to define and analyze dynamic pathway models based on non-linear kinetic rate equations. The design of the MMT software differs from other available pathway modeling tools in a variety of things. With respect to model definition, the tool has no limitations in dimension and it is based on a relational database that stores all model information and results . In order to allow definition of a large number of models the tool has a structured approach that allows to build groups of models and groups of parameter fittings . Groups share e.g. the metabolic pathway or kinetic equations . With respect to simulation and parameter fitting, MMT provides high flexibility . Parameters can e.g. be optimized or set to experimental data values or initial conditions can be optimized. Stoichiometric coefficients can also be subject to parameter fitting . Additionally simulation time is variable and artificial noise can be added to the calculated values to simulate experimental data. The software creates a CCode with the System of differential equations and also with the explicit derivatives with respect to initial conditions and parameters, thus providing a complete set of sensitivity functions . The tool allows not only visualization of the solution of the differential equations but also of each individual flux between compounds . These values correspond to the kinetic equations over time and are helpful in analyzing simulation and parameter fitting results . MMT was applied to the central metabolic pathways of Escherichia coli. Data from fast sampling experiments (Glucose pulse experiments, 4 samples per second over 40 seconds) was used for parameter fitting. Some metabolic regulation phenomena in relation to these experiments are discussed in this thesis . |