Minimal metabolic pathway structure is consistent with associated biomolecular interactions

Aarash Bordbar, Harish Nagarajan, Nathan E. Lewis, Haythem Latif, Ali Ebrahim, Stephen Federowicz, Jan Schellenberger, Bernhard Palsson

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Abstract

Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated.
Original languageEnglish
JournalMolecular Systems Biology
Volume10
Issue number7
Number of pages16
ISSN1744-4292
Publication statusPublished - 2014

Keywords

  • BIOCHEMISTRY
  • ESCHERICHIA-COLI
  • FUNCTIONAL-CHARACTERIZATION
  • EXTREME PATHWAYS
  • GENE ONTOLOGY
  • DATA SETS
  • GENOME
  • NETWORKS
  • YEAST
  • CELL
  • RECONSTRUCTION
  • constraint-based modeling
  • genetic interactions
  • pathway analysis
  • protein-protein interactions
  • transcriptional regulatory networks

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