title: Qualitative modelling of regulated metabolic pathways: application to the tryptophan biosynthesis in E.coli.
abstract: BACKGROUND
  The integrated dynamical modelling of mixed metabolic/genetic networks constitutes one of the challenges of systems biology. Furthermore, as most of available data about genetic and metabolic regulations are qualitative, there is a pressing need for rigorous qualitative mathematical approaches.
  
  
  RESULTS
  On the basis of two established formalisms, the logical modelling of genetic regulatory networks and the Petri net modelling of metabolic networks, we propose a systematic approach for the modelling of regulated metabolic networks. This approach leans on previous work defining a systematic procedure to translate logical regulatory graphs into standard (discrete) Petri nets (PNs). This approach is illustrated by the qualitative modelling of the biosynthesis of tryptophan (Trp) in Escherichia coli, taking into account two types of regulatory feedbacks: the direct inhibition of the first enzyme of the pathway by the final product of the pathway, and the transcriptional inhibition of the Trp operon by the Trp-repressor complex. On the basis of this integrated PN model, we further indicate how available dynamical analysis tools can be applied to obtain significant insights in the behaviour of the system.
  
  
  BACKGROUND
  The software GINsim for the logical modelling of genetic regulatory networks together with the PN model of the regulated Trp biosynthesis pathway are available at: http://gin.univ-mrs.fr/GINsim.
authors.affiliation: Institut de Biologie du Développement de Marseille Campus de Luminy, Marseille cedex 9, France.
authors.forename: E
authors.initials: E
authors.lastname: Simão
authors.forename: E
authors.initials: E
authors.lastname: Remy
authors.forename: D
authors.initials: D
authors.lastname: Thieffry
authors.forename: C
authors.initials: C
authors.lastname: Chaouiya
mesh_terms: D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008954:Models, Biological; D016571:Neural Networks, Computer; D015398:Signal Transduction / Q000502:physiology*; D014364:Tryptophan / Q000096:biosynthesis*
chemical_list: D029968:Escherichia coli Proteins; D014364:Tryptophan