Tuesday, July 28, 2009 - 11:00 AM
S67
Integrative mechanistic modeling of C. glutamicum Lysine producer: Making sense of quantitative multi-omics data
Stephan Noack, Marco Oldiges, and Wolfgang Wiechert. Institute of Biotechnology 2, Research Centre Jülich, Leo-Brandt-Str, Juelich, Germany
The quantitative understanding of regulatory principles in microbial networks is one major aim in Systems Biology. To achieve this goal two main prerequisites must be fulfilled. Firstly, multi-omics data providing the full range of information along all levels of regulation (genome, proteome, metabolome) are needed. Secondly, integrative model approaches must be developed in order to evaluate the huge amount of data obtained by multi-omics analytics. In the project “Systems biology of microbial amino acid producers” (SysMAP) several German research teams worked together to fulfill these tasks. Cultivations of different genetically modified strains of C. glutamicum were performed in continuous and fed-batch mode under varying quasi steady state conditions. Samples were analyzed using different omics technologies to obtain (i) genome wide transcriptome data from Affymetrix chips, (ii) enzyme activities using enzyme assays, (iii) metabolite pool sizes of the central metabolic pathways applying LC-MS/MS analytics and (iv) metabolic fluxes in these pathways applying 13C metabolic flux analysis.
The available data set is used for building up a mechanistic model of C. glutamicum that focuses on the description of TCA-cycle regulation. For the integration of the omics datasets a vertical model approach is formulated that allows the quantification of regulatory interactions on the different omics levels. These can be visually explored in the network context leading to novel insights into regulatory principles of C. glutamicum. Moreover the application of metabolic control analysis leads to model based predictions for strain improvement and further experimental investigations.
The available data set is used for building up a mechanistic model of C. glutamicum that focuses on the description of TCA-cycle regulation. For the integration of the omics datasets a vertical model approach is formulated that allows the quantification of regulatory interactions on the different omics levels. These can be visually explored in the network context leading to novel insights into regulatory principles of C. glutamicum. Moreover the application of metabolic control analysis leads to model based predictions for strain improvement and further experimental investigations.
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See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)