Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism

PLoS One. 2015 Jun 18;10(6):e0129837. doi: 10.1371/journal.pone.0129837. eCollection 2015.

Abstract

NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / metabolism*
  • Computer Simulation
  • Cyclization
  • Escherichia coli / enzymology
  • Escherichia coli / metabolism*
  • Metabolic Networks and Pathways*
  • Models, Biological
  • NADP / metabolism*
  • Oxidation-Reduction
  • Thermodynamics

Substances

  • NADP
  • Carbon

Grants and funding

This work was supported by the Chinese National Natural Science Foundation (grant 31200626, 31460233, 31372402), the Biology Key Subject Construction of Anhui (2014SKQJ017), the Programme for Changjiang Scholars and the Innovative Research Teams at the University (PCSIRT–1227), the Initial Fund for the Key Laboratory of Guizhou Province (Grant no. 2011–4005), the Guizhou Lianhe Foundation, LKS(2012)22, the Initial Fund for collaborative Innovation Center of Guizhou Province ([2014]04).