Genome-scale reconstruction of the streptococcus pyogenes M49 metabolic network reveals growth requirements and indicates potential drug targets

Genome-scale metabolic models comprise stoichiometric relations between metabolites, as well as associations between genes and metabolic reactions and facilitate the analysis of metabolism. We computationally reconstructed the metabolic network of the lactic acid bacterium Streptococcus pyogenes M49...

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Main Authors: Levering, Jennifer (Author) , Fiedler, Tomas (Author) , Sieg, Antje (Author) , van Grinsven, Koen W. A. (Author) , Hering, Silvio (Author) , Veith, Nadine (Author) , Olivier, Brett G. (Author) , Klett, Lara C. (Author) , Hugenholtz, Jeroen (Author) , Teusink, Bas (Author) , Kreikemeyer, Bernd (Author) , Kummer, Ursula (Author)
Format: Article (Journal)
Language:English
Published: 10 March 2016
In: Journal of biotechnology
Year: 2016, Volume: 232, Pages: 25-37
ISSN:1873-4863
DOI:10.1016/j.jbiotec.2016.01.035
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jbiotec.2016.01.035
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0168165616300074
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Author Notes:Jennifer Levering, Tomas Fiedler, Antje Sieg, Koen W.A. van Grinsven, Silvio Hering, Nadine Veith, Brett G. Olivier, Lara Klett, Jeroen Hugenholtz, Bas Teusink, Bernd Kreikemeyer, Ursula Kummer
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Summary:Genome-scale metabolic models comprise stoichiometric relations between metabolites, as well as associations between genes and metabolic reactions and facilitate the analysis of metabolism. We computationally reconstructed the metabolic network of the lactic acid bacterium Streptococcus pyogenes M49. Initially, we based the reconstruction on genome annotations and already existing and curated metabolic networks of Bacillus subtilis, Escherichia coli, Lactobacillus plantarum and Lactococcus lactis. This initial draft was manually curated with the final reconstruction accounting for 480 genes associated with 576 reactions and 558 metabolites. In order to constrain the model further, we performed growth experiments of wild type and arcA deletion strains of S. pyogenes M49 in a chemically defined medium and calculated nutrient uptake and production fluxes. We additionally performed amino acid auxotrophy experiments to test the consistency of the model. The established genome-scale model can be used to understand the growth requirements of the human pathogen S. pyogenes and define optimal and suboptimal conditions, but also to describe differences and similarities between S. pyogenes and related lactic acid bacteria such as L. lactis in order to find strategies to reduce the growth of the pathogen and propose drug targets.
Item Description:Gesehen am 09.06.2020
Physical Description:Online Resource
ISSN:1873-4863
DOI:10.1016/j.jbiotec.2016.01.035