title: Exploring the diversity of complex metabolic networks.
abstract: BACKGROUND
  Metabolism, the network of chemical reactions that make life possible, is one of the most complex processes in nature. We describe here the development of a computational approach for the identification of every possible biochemical reaction from a given set of enzyme reaction rules that allows the de novo synthesis of metabolic pathways composed of these reactions, and the evaluation of these novel pathways with respect to their thermodynamic properties.
  
  
  RESULTS
  We applied this framework to the analysis of the aromatic amino acid pathways and discovered almost 75,000 novel biochemical routes from chorismate to phenylalanine, more than 350,000 from chorismate to tyrosine, but only 13 from chorismate to tryptophan. Thermodynamic analysis of these pathways suggests that the native pathways are thermodynamically more favorable than the alternative possible pathways. The pathways generated involve compounds that exist in biological databases, as well as compounds that exist in chemical databases and novel compounds, suggesting novel biochemical routes for these compounds and the existence of biochemical compounds that remain to be discovered or synthesized through enzyme and pathway engineering.
  
  
  BACKGROUND
  Framework will be available via web interface at http://systemsbiology.northwestern.edu/BNICE (site under construction).
  
  
  BACKGROUND
  vassily@northwestern.edu or broadbelt@northwestern.edu
  
  
  BACKGROUND
  http://systemsbiology.northwestern.edu/BNICE/publications.
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, IL, USA. vassily@northwestern.edu
authors.forename: Vassily
authors.initials: V
authors.lastname: Hatzimanikatis
authors.forename: Chunhui
authors.initials: C
authors.lastname: Li
authors.forename: Justin A
authors.initials: JA
authors.lastname: Ionita
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Henry
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Jankowski
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Broadbelt
mesh_terms: D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000818:Animals; D044822:Biodiversity; D003196:Computer Graphics; D003198:Computer Simulation; D004734:Energy Metabolism / Q000502:physiology*; D005240:Feasibility Studies; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014584:User-Computer Interface
chemical_list: D024322:Amino Acids, Aromatic; D009097:Multienzyme Complexes