Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0
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Date
2022
Authors
Domenzain, Ivan
Sánchez, Benjamín
Anton, Mihail
Kerkhoven, Eduard J.
Millan-Oropeza, Aaron
Henry, Celine
Siewers, Verena
Morrissey, John P.
Sonnenschein, Nikolaus
Nielsen, Jens
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature
Published Version
Abstract
Genome-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.
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Keywords
GEMs , Genome-scale metabolic models , GECKO 2.0
Citation
Domenzain, 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/s41467-022-31421-1