Modeling Method for Increased Precision and Scope of Directly Measurable Fluxes at a Genome-Scale

  • McCloskey D
  • Young J
  • Xu S
 et al. 
  • 38

    Readers

    Mendeley users who have this article in their library.
  • 9

    Citations

    Citations of this article.

Abstract

Metabolic flux analysis (MFA) is considered to be the gold standard for determining the intracellular flux distribution of biological systems. The majority of work using MFA has been limited to core models of metabolism due to challenges in implementing genome-scale MFA and the undesirable trade-off between increased scope and decreased precision in flux estimations. This work presents a tunable workflow for expanding the scope of MFA to the genome-scale without trade-offsin flux precision. The genome-scale MFA model presented here, iDM2014, accounts for 537 net reactions, which includes the core pathways of traditional MFA models and also covers the additional pathways of purine, pyrimidine, isoprenoid, methionine, riboflavin, coenzyme A, and folate, as well as other biosynthetic pathways. When evaluating the iDM2014 using a set of measured intracellular intermediate and cofactor mass isotopomer distributions (MIDs),1 it was found that a total of 232 net fluxes of central and peripheral metabolism could be resolved in the E. coli network. The increase in scope was shown to cover the full biosynthetic route to an expanded set of bioproduction pathways, which should facilitate applications such as the design of more complex bioprocessing strains and aid in identifying new antimicrobials. Importantly, it was found that there was no loss in precision of core fluxes when compared to a traditional core model, and additionally there was an overall increase in precision when considering all observable reactions

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Jamey YoungVanderbilt University

    Follow
  • Douglas McCloskey

  • Sibei Xu

  • Bernhard O. Palsson

  • Adam M. Feist

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free