Blank-2005-Large-scale 13C-flux.pdfVIP

co m m ent review s repo rts depo sited research refereed research interactio ns info rm atio nOpen Access2005Blanket l.Volume 6, Issue 6, Article R49Research 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 Zürich, 8093 Zürich, Switzerland. Correspondence: Uwe Sauer. E-mail: sauer@biotech.biol.ethz.ch ? 2005 Blank et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Large-scale 13C-flux analysis in yeastpGenome-sca e 13supC/sup-flux analysis in Saccharomyces cerevisiae revealed that the apparent dispensability of knockout mutants with metabolic function can be expl ined by gene inactivity under a pa ticular condi ion, by n twork r dundancy through dupli-c ted genes or by lternative pathways./p 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 wer