Reconstruction and analysis of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis

Anne Goelzer¹ , Fadia Bekkal Brikci¹ , Isabelle Martin-Verstraete²^,3 , Philippe Noirot⁴ , Philippe Bessières¹ , Stéphane Aymerich⁵ and Vincent Fromion¹

¹Unité Mathématique, Informatique et Génomes, Institut National Recherche Agronomique, UR1077, F-78350 Jouy-en-Josas, France

²Unité de Génétique des Génomes Bactériens, Institut Pasteur, URA CNRS 2171, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France

³Unité de Formation et de Recherche de Biochimie, Université Paris 7-Denis Diderot, 2 place Jussieu, 75251 Paris, France

⁴Unité Génétique Microbienne, Institut National Recherche Agronomique, F-78350 Jouy-en-Josas, France

⁵Microbiologie et Génétique Moléculaire, Institut National Recherche Agronomique Paris-Grignon, CNRS (UMR2585) INRA (UMR1238), F-78850 Thiverval-Grignon, France

author email corresponding author email

BMC Systems Biology 2008, 2:20doi:10.1186/1752-0509-2-20


Published:	26 February 2008

Abstract

Background

Few genome-scale models of organisms focus on the regulatory networks and none of them integrates all known levels of regulation. In particular, the regulations involving metabolite pools are often neglected. However, metabolite pools link the metabolic to the genetic network through genetic regulations, including those involving effectors of transcription factors or riboswitches. Consequently, they play pivotal roles in the global organization of the genetic and metabolic regulatory networks.

Results

We report the manually curated reconstruction of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis (transcriptional, translational and post-translational regulations and modulation of enzymatic activities). We provide a systematic graphic representation of regulations of each metabolic pathway based on the central role of metabolites in regulation. We show that the complex regulatory network of B. subtilis can be decomposed as sets of locally regulated modules, which are coordinated by global regulators.

Conclusion

This work reveals the strong involvement of metabolite pools in the general regulation of the metabolic network. Breaking the metabolic network down into modules based on the control of metabolite pools reveals the functional organization of the genetic and metabolic regulatory networks of B. subtilis.