Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast. | Research Open Access Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast Lars M Blank Lars Kuepfer and Uwe Sauer Address Institute of Biotechnology ETH Zurich 8093 Zurich Switzerland. Correspondence Uwe Sauer. E-mail sauer@ Published 17 May 2005 Genome Biology 2005 6 R49 doi 186 gb-2005-6-6-r49 The electronic version of this article is the complete one and can be found online at http 2005 6 6 R49 Received 1 February 2005 Revised 8 March 2005 Accepted 6 April 2005 2005 Blank et al. licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background Quantification of intracellular metabolite fluxes by 13C-tracer experiments is maturing into a routine higher-throughput analysis. The question now arises as to which mutants should be analyzed. Here we identify key experiments in a systems biology approach with a genome-scale model of Saccharomyces cerevisiae metabolism thereby reducing the workload for experimental network analyses and functional genomics. Results Genome-scale 13C flux analysis revealed that about half of the 745 biochemical reactions were active during growth on glucose but that alternative pathways exist for only 51 gene-encoded reactions with significant flux. These flexible reactions identified in silico are key targets for experimental flux analysis and we present the first large-scale metabolic flux data for yeast covering half of these mutants during growth on glucose. The metabolic lesions were often counteracted by flux rerouting but knockout of cofactor-dependent reactions as in the adhl ald6 cox5A fuml mdhl pdal and zwfl mutations caused flux responses in more distant parts of the network. By
