Basic pathway decomposition of biochemical reaction networks within growing cells

iScience. 2023 Nov 22;27(1):108506. doi: 10.1016/j.isci.2023.108506. eCollection 2024 Jan 19.

Abstract

This contribution treats linear, steady-state dynamics for a metabolic network within a growing cell. Admissible steady-state reaction fluxes are assumed to form a pointed, convex, polyhedral, conical subset of the stoichiometric null-space. A solution of the problem is defined to consist of a linear basis for the stoichiometric null-space consisting of admissible fluxes called basic pathways. The algorithm used to construct the set of basic pathways scales as a polynomial of the system size in contrast to the NP-hard algorithms employed in the traditional notions of solution named extreme pathways, elementary flux modes, MEMos, and MinSpan, and that therefore suffer from the curse of dimensionality. The basic pathways approach is applied to a metabolic network consisting of a simplified version of the TCA cycle coupled to glycolysis highlighting that each basic pathway has a readily understood chemical interpretation. Generic admissible pathways are simply expressed in terms of basic pathways.

Keywords: Biological sciences; Metabolic engineering; Network.