Forster-2003-Genome-scale reconst.pdf

Genome-Scale Reconstruction of the Saccharomyces cerevisiae Metabolic Network Jochen Fo?rster,1,3,4 Iman Famili,2,4 Patrick Fu,2 Bernhard ?. Palsson,2 and Jens Nielsen1,5 1Center for Process Biotechnology, BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby, Denmark; 2Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA The metabolic network in the yeast Saccharomyces cerevisiae was reconstructed using currently available genomic, biochemical, and physiological information. The metabolic reactions were compartmentalized between the cytosol and the mitochondria, and transport steps between the compartments and the environment were included. A total of 708 structural open reading frames (ORFs) were accounted for in the reconstructed network, corresponding to 1035 metabolic reactions. Further, 140 reactions were included on the basis of biochemical evidence resulting in a genome-scale reconstructed metabolic network containing 1175 metabolic reactions and 584 metabolites. The number of gene functions included in the reconstructed network corresponds to ～16% of all characterized ORFs in S. cerevisiae. Using the reconstructed network, the metabolic capabilities of S. cerevisiae were calculated and compared with Escherichia coli. The reconstructed metabolic network is the first comprehensive network for a eukaryotic organism, and it may be used as the basis for in silico analysis of phenotypic functions. [Supplemental material is available online at . The detailed genome-scale reconstructed model of Saccharomyces cerevisiae can be found at http://www.cpb.dtu.dk/models/yeastmodel.html or http://geneticcircuits. /organisms/yeast.html.] Baker’s yeast, Saccharomyces cerevisiae, was the first eukaryotic genome that was fully sequenced, annotated, and made pub- licly available. (Goffeau 1997). Along with its industrial im- portance, S. cerevisiae serves as a model organism for under- standing and engineering eukaryotic ce