K-FIT: An accelerated kinetic parameterization algorithm using steady-state fluxomic data

Saratram Gopalakrishnan, Satyakam Dash, Costas Maranas

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Kinetic models predict the metabolic flows by directly linking metabolite concentrations and enzyme levels to reaction fluxes. Robust parameterization of organism-level kinetic models that faithfully reproduce the effect of different genetic or environmental perturbations remains an open challenge due to the intractability of existing algorithms. This paper introduces Kinetics-based Fluxomics Integration Tool (K-FIT), a robust kinetic parameterization workflow that leverages a novel decomposition approach to identify steady-state fluxes in response to genetic perturbations followed by a gradient-based update of kinetic parameters until predictions simultaneously agree with the fluxomic data in all perturbed metabolic networks. The applicability of K-FIT to large-scale models is demonstrated by parameterizing an expanded kinetic model for E. coli (307 reactions and 258 metabolites) using fluxomic data from six mutants. The achieved thousand-fold speed-up afforded by K-FIT over meta-heuristic approaches is transformational enabling follow-up robustness of inference analyses and optimal design of experiments to inform metabolic engineering strategies.

Original languageEnglish (US)
Pages (from-to)197-205
Number of pages9
JournalMetabolic engineering
Volume61
DOIs
StatePublished - Sep 2020

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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