tailieunhanh - Báo cáo khoa học: Reconstruction of the central carbon metabolism of Aspergillus niger

The topology of central carbon metabolism ofAspergillus nigerwas identified and the metabolic network reconstruc-ted, by integrating genomic, biochemical and physiological information available for this microorganism and other related fungi. The reconstructed network may serve as a valuabledatabase for annotationof genes identified in future genome sequencing projects on aspergilli. Based on the metabolic reconstruction, a stoichiometric model was set up that includes 284metabolites and335reactions,. | Eur. J. Biochem. 270 4243-4253 2003 FEBS 2003 doi Reconstruction of the central carbon metabolism of Aspergillus niger Helga David Mats Akesson and Jens Nielsen Center for Process Biotechnology BioCentrum-DTU Building 223 Technical University of Denmark DK-2800 Kgs. Lyngby Denmark The topology of central carbon metabolism of Aspergillus niger was identified and the metabolic network reconstructed by integrating genomic biochemical and physiological information available for this microorganism and other related fungi. The reconstructed network may serve as a valuable database for annotation of genes identified in future genome sequencing projects on aspergilli. Based on the metabolic reconstruction a stoichiometric model was set up that includes 284 metabolites and 335 reactions of which 268 represent biochemical conversions and 67 represent transport processes between the different intracellular compartments and between the cell and the extracellular medium. The stoichiometry of the metabolic reactions was used in combination with biosynthetic requirements for growth and pseudo-steady state mass balances over intracellular metabolites for the quantification of metabolic fluxes using metabolite balancing. This framework was employed to perform an in silico characterisation of the phenotypic behaviour of A. niger grown on different carbon sources. The effects on growth of single reaction deletions were assessed and essential biochemical reactions were identified for different carbon sources. Furthermore application of the stoichiometric model for assessing the metabolic capabilities of A. niger to produce metabolites was evaluated by using succinate production as a case study. Keywords Aspergillus niger metabolic reconstruction flux balance analysis functional genomics. Filamentous fungi are important organisms for the production of industrial enzymes speciality chemicals and pharmaceuticals. Moreover they play a major role for human