Quantifying the propagation of parametric uncertainty on flux balance analysis

Hoang V. Dinh, Debolina Sarkar, Costas D. Maranas

Research output: Contribution to journalArticlepeer-review

Abstract

Flux balance analysis (FBA) and associated techniques operating on stoichiometric genome-scale metabolic models play a central role in quantifying metabolic flows and constraining feasible phenotypes. At the heart of these methods lie two important assumptions: (i) the biomass precursors and energy requirements neither change in response to growth conditions nor environmental/genetic perturbations, and (ii) metabolite production and consumption rates are equal at all times (i.e., steady-state). Despite the stringency of these two assumptions, FBA has been shown to be surprisingly robust at predicting cellular phenotypes. In this paper, we formally assess the impact of these two assumptions on FBA results by quantifying how uncertainty in biomass reaction coefficients, and departures from steady-state due to temporal fluctuations could propagate to FBA results. In the first case, conditional sampling of parameter space is required to re-weigh the biomass reaction so as the molecular weight remains equal to 1 g mmol−1, and in the second case, metabolite (and elemental) pool conservation must be imposed under temporally varying conditions. Results confirm the importance of enforcing the aforementioned constraints and explain the robustness of FBA biomass yield predictions.

Original languageEnglish (US)
Pages (from-to)26-39
Number of pages14
JournalMetabolic engineering
Volume69
DOIs
StatePublished - Jan 2022

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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