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J Biotechnol. 2016 Aug 20;232:25-37. doi: 10.1016/j.jbiotec.2016.01.035. Epub 2016 Mar 10.

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

Author information

1
Department of Modeling of Biological Processes, COS Heidelberg/BioQuant, Heidelberg University, Heidelberg, Germany. Electronic address: jlevering@ucsd.edu.
2
Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Centre, Rostock, Germany. Electronic address: tomas.fiedler@med.uni-rostock.de.
3
Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Centre, Rostock, Germany.
4
Laboratory for Microbiology, Swammerdam Institute for Life Sciences, Amsterdam, The Netherlands.
5
Department of Modeling of Biological Processes, COS Heidelberg/BioQuant, Heidelberg University, Heidelberg, Germany.
6
Amsterdam Insitute for Molecules, Medicines and Systems, VU Amsterdam, The Netherlands.

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.

KEYWORDS:

Amino acid auxotrophies; Genome-scale metabolic model; Lactic acid bacteria; Metabolism; Streptococcus pyogenes

PMID:
26970054
DOI:
10.1016/j.jbiotec.2016.01.035
[Indexed for MEDLINE]

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