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Nookaew2008_Yeast_MetabolicNetwork_iIN800


ABSTRACT: This is a reconstruction of the metabolic network of the yeast Saccharomyces cerevisiae as described in the article: The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism. Nookaew I, Jewett MC, Meechai A, Thammarongtham C, Laoteng K, Cheevadhanarak S, Nielsen J, Bhumiratana S. BMC Syst Biol. 2008 Aug 7;2:71; PMID: 18687109 ,doi: 10.1186/1752-0509-2-71 Abstract: BACKGROUND: Up to now, there have been three published versions of a yeast genome-scale metabolic model: iFF708, iND750 and iLL672. All three models, however, lack a detailed description of lipid metabolism and thus are unable to be used as integrated scaffolds for gaining insights into lipid metabolism from multilevel omic measurement technologies (e.g. genome-wide mRNA levels). To overcome this limitation, we reconstructed a new version of the Saccharomyces cerevisiae genome-scale model, iIN800 that includes a more rigorous and detailed description of lipid metabolism. RESULTS: The reconstructed metabolic model comprises 1446 reactions and 1013 metabolites. Beyond incorporating new reactions involved in lipid metabolism, we also present new biomass equations that improve the predictive power of flux balance analysis simulations. Predictions of both growth capability and large scale in silico single gene deletions by iIN800 were consistent with experimental data. In addition, 13C-labeling experiments validated the new biomass equations and calculated intracellular fluxes. To demonstrate the applicability of iIN800, we show that the model can be used as a scaffold to reveal the regulatory importance of lipid metabolism precursors and intermediates that would have been missed in previous models from transcriptome datasets. CONCLUSION: Performing integrated analyses using iIN800 as a network scaffold is shown to be a valuable tool for elucidating the behavior of complex metabolic networks, particularly for identifying regulatory targets in lipid metabolism that can be used for industrial applications or for understanding lipid disease states. The SBML was downloaded from the BioMet Toolbox page( http://129.16.106.142/models.php?c=S.cerevisiae ) of Jens Nielsen's Lab for Systems Biology at Chalmers University ( http://www.sysbio.se/ ). The parameters LOWER_BOUND and UPPER_BOUND were added as defined in the BioOpt file available from the same page. One error was corrected R_PIxtO (Excretion of phosphate) LOWER_BOUND was changed from 1000 to 0. Parameters FLUX_VALUE were then calculated as defined in "Flux balance analysis: a geometric perspective.", Smallbone K and Simeonidis E, 2009 (J Theor Biol. 2009;258(2):311-5, pmid: 19490860 ). Technical notes: The compartments included here have no volume defined; there are no reliable estimates available for those volumes yet. There are no kinetic functions defined for the reactions because this model only represents the chemical structure of the network (stoichiometry). Reactions for uptake and excretion are defined for some of the metabolites. All uptake reactions are constrained to zero flux and all excretion reactions are unconstrained. All genes are assigned to the cytosol. This has no physiological meaning, but it is necessary for the structure of the model. Biomass equations are available for carbon-limited and nitrogen-limited growth. The nitrogen-limited biomass equation is constrained to zero flux. A few reactions are meant to be used to simulate the effect of for example increased ATP production. They are constrained to zero flux. This SBML representation of the yeast metabolic network is made available under the Creative Commons Attribution-Share Alike 3.0 Unported Licence (see www.creativecommons.org ). This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Kieran Smallbone  

PROVIDER: MODEL1002240000 | BioModels | 2005-01-01

REPOSITORIES: BioModels

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Publications

The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism.

Nookaew Intawat I   Jewett Michael C MC   Meechai Asawin A   Thammarongtham Chinae C   Laoteng Kobkul K   Cheevadhanarak Supapon S   Nielsen Jens J   Bhumiratana Sakarindr S  

BMC systems biology 20080807


<h4>Background</h4>Up to now, there have been three published versions of a yeast genome-scale metabolic model: iFF708, iND750 and iLL672. All three models, however, lack a detailed description of lipid metabolism and thus are unable to be used as integrated scaffolds for gaining insights into lipid metabolism from multilevel omic measurement technologies (e.g. genome-wide mRNA levels). To overcome this limitation, we reconstructed a new version of the Saccharomyces cerevisiae genome-scale model  ...[more]

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