lumpGEM: Systematic generation of subnetworks and elementally balanced lumped reactions for the biosynthesis of target metabolites

PLoS Comput Biol. 2017 Jul 20;13(7):e1005513. doi: 10.1371/journal.pcbi.1005513. eCollection 2017 Jul.

Abstract

In the post-genomic era, Genome-scale metabolic networks (GEMs) have emerged as invaluable tools to understand metabolic capabilities of organisms. Different parts of these metabolic networks are defined as subsystems/pathways, which are sets of functional roles to implement a specific biological process or structural complex, such as glycolysis and TCA cycle. Subsystem/pathway definition is also employed to delineate the biosynthetic routes that produce biomass building blocks. In databases, such as MetaCyc and SEED, these representations are composed of linear routes from precursors to target biomass building blocks. However, this approach cannot capture the nested, complex nature of GEMs. Here we implemented an algorithm, lumpGEM, which generates biosynthetic subnetworks composed of reactions that can synthesize a target metabolite from a set of defined core precursor metabolites. lumpGEM captures balanced subnetworks, which account for the fate of all metabolites along the synthesis routes, thus encapsulating reactions from various subsystems/pathways to balance these metabolites in the metabolic network. Moreover, lumpGEM collapses these subnetworks into elementally balanced lumped reactions that specify the cost of all precursor metabolites and cofactors. It also generates alternative subnetworks and lumped reactions for the same metabolite, accounting for the flexibility of organisms. lumpGEM is applicable to any GEM and any target metabolite defined in the network. Lumped reactions generated by lumpGEM can be also used to generate properly balanced reduced core metabolic models.

MeSH terms

  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Genomics / methods*
  • Metabolic Networks and Pathways / genetics*
  • Metabolic Networks and Pathways / physiology*
  • Models, Biological*
  • Systems Biology / methods*

Grants and funding

The authors received no specific funding for this work.