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Applied Mathematics
Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based analysis of a genome-scale reconstructed metabolic network
*Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412; and Center for Process Biotechnology, BioCentrum-DTU, Technical University of Denmark, 2800 Lyngby, Denmark
Communicated by Yuan-Cheng B. Fung, University of California at San Diego, La Jolla, CA, September 10, 200310. (received for review June 19, 2003)
Full genome sequences of prokaryotic organisms have led to reconstruction of genome-scale metabolic networks and in silico computation of their integrated functions. The first genome-scale metabolic reconstruction for a eukaryotic cell, Saccharomyces cerevisiae, consisting of 1,175 metabolic reactions and 733 metabolites, has appeared. A constraint-based in silico analysis procedure was used to compute properties of the S. cerevisiae metabolic network. The computed number of ATP molecules produced per pair of electrons donated to the electron transport system (ETS) and energy-maintenance requirements were quantitatively in agreement with experimental results. Computed whole-cell functions of growth and metabolic by-product secretion in aerobic and anaerobic culture were consistent with experimental data, and thus mRNA expression profiles during metabolic shifts were computed. The computed consequences of gene knockouts on growth phenotypes were consistent with experimental observations. Thus, constraint-based analysis of a genome-scale metabolic network for the eukaryotic S. cerevisiae allows for computation of its integrated functions, producing in silico results that were consistent with observed phenotypic functions for 
70–80% of the conditions considered.
I.F. and J.F. contributed equally to this work.
Present address: Fluxome Sciences A/S, Søltofts Plads, Building 223, Technical University of Denmark, 2800 Lyngby, Denmark.
¶ To whom correspondence should be addressed. E-mail: palsson{at}ucsd.edu.
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