Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0

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dc.contributor.authorDomenzain, Ivanen
dc.contributor.authorSánchez, Benjamínen
dc.contributor.authorAnton, Mihailen
dc.contributor.authorKerkhoven, Eduard J.en
dc.contributor.authorMillan-Oropeza, Aaronen
dc.contributor.authorHenry, Celineen
dc.contributor.authorSiewers, Verenaen
dc.contributor.authorMorrissey, John P.en
dc.contributor.authorSonnenschein, Nikolausen
dc.contributor.authorNielsen, Jensen
dc.contributor.funderHorizon 2020 Framework Programmeen
dc.contributor.funderKnut och Alice Wallenbergs Stiftelseen
dc.contributor.funderNovo Nordisk Fondenen
dc.date.accessioned2024-09-05T11:35:37Z
dc.date.available2024-09-05T11:35:37Z
dc.date.issued2022en
dc.description.abstractGenome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into such models was first enabled by the GECKO toolbox, allowing the study of phenotypes constrained by protein limitations. Here, we upgrade the toolbox in order to enhance models with enzyme and proteomics constraints for any organism with a compatible GEM reconstruction. With this, enzyme-constrained models for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus are generated to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions reveal that upregulation and high saturation of enzymes in amino acid metabolism are common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO is expanded with an automated framework for continuous and version-controlled update of enzyme-constrained GEMs, also producing such models for Escherichia coli and Homo sapiens. In this work, we facilitate the utilization of enzyme-constrained GEMs in basic science, metabolic engineering and synthetic biology purposes.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid3766en
dc.identifier.citationDomenzain, I., Sánchez, B., Anton, M., Kerkhoven, E.J., Millán-Oropeza, A., Henry, C., Siewers, V., Morrissey, J.P., Sonnenschein, N. and Nielsen, J. (2022) ‘Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0’, Nature Communications, 13(1), 3766 (13pp). doi: 10.1038/s41467-022-31421-1en
dc.identifier.doi10.1038/s41467-022-31421-1en
dc.identifier.eissn2041-1723en
dc.identifier.endpage13en
dc.identifier.issued1en
dc.identifier.journaltitleNature Communicationsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/16302
dc.identifier.volume13en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::RIA/720824/EU/Model-Based Construction And Optimisation Of Versatile Chassis Yeast Strains For Production Of Valuable Lipid And Aromatic Compounds/CHASSYen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::RIA/686070/EU/Bioinformatics Services for Data-Driven Design of Cell Factories and Communities/DD-DeCaFen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::IA/760798/EU/OLEAginous yeast platforms for FINE chemicals/OLEFINEen
dc.rights© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectGEMsen
dc.subjectGenome-scale metabolic modelsen
dc.subjectGECKO 2.0en
dc.titleReconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0en
dc.typeArticle (peer-reviewed)en
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