title: Genome-scale reconstruction of the Streptococcus pyogenes M49 metabolic network reveals growth requirements and indicates potential drug targets.
abstract: 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.
authors.affiliation: Department of Modeling of Biological Processes, COS Heidelberg/BioQuant, Heidelberg University, Heidelberg, Germany. Electronic address: jlevering@ucsd.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Levering
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Centre, Rostock, Germany. Electronic address: tomas.fiedler@med.uni-rostock.de.
authors.forename: Tomas
authors.initials: T
authors.lastname: Fiedler
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Centre, Rostock, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Sieg
authors.affiliation: Laboratory for Microbiology, Swammerdam Institute for Life Sciences, Amsterdam, The Netherlands.
authors.forename: Koen W A
authors.initials: KW
authors.lastname: van Grinsven
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Centre, Rostock, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Hering
authors.affiliation: Department of Modeling of Biological Processes, COS Heidelberg/BioQuant, Heidelberg University, Heidelberg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Veith
authors.affiliation: Amsterdam Insitute for Molecules, Medicines and Systems, VU Amsterdam, The Netherlands.
authors.forename: Brett G
authors.initials: BG
authors.lastname: Olivier
authors.affiliation: Department of Modeling of Biological Processes, COS Heidelberg/BioQuant, Heidelberg University, Heidelberg, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Klett
authors.affiliation: Laboratory for Microbiology, Swammerdam Institute for Life Sciences, Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hugenholtz
authors.affiliation: Amsterdam Insitute for Molecules, Medicines and Systems, VU Amsterdam, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Teusink
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Centre, Rostock, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer
authors.affiliation: Department of Modeling of Biological Processes, COS Heidelberg/BioQuant, Heidelberg University, Heidelberg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kummer
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D016680:Genome, Bacterial / Q000235:genetics*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008957:Models, Genetic; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000596:Amino Acids
keywords: Amino acid auxotrophies; Genome-scale metabolic model; Lactic acid bacteria; Metabolism; Streptococcus pyogenes