Essentiality landscape of metabolic networks

TL;DR

This study quantifies the essentiality of metabolic reactions across hundreds of species using flux balance analysis, revealing patterns related to reaction age and species evolution, and highlighting the redundancy and importance of certain reactions.

Contribution

It provides a large-scale, cross-species analysis of reaction essentiality and introduces the concept of reaction and species age correlations with essentiality.

Findings

Approximately 10% of reactions are essential for growth.

Older reactions tend to be more essential, especially in younger species.

Most reactions are redundant, indicating robustness in metabolic networks.

Abstract

Local perturbations of individual metabolic reactions may result in different levels of lethality, depending on their roles in metabolism and the size of subsequent cascades induced by their failure. Moreover, essentiality of individual metabolic reactions may show large variations within and across species. Here we quantify their essentialities in hundreds of species by computing the growth rate after removal of individual and pairs of reactions by flux balance analysis. We find that about 10% of reactions are essential, i.e., growth stops without them, and most of the remaining reactions are redundant in the metabolic network of each species. This large-scale and cross-species study allows us to determine ad hoc ages of each reaction and species. We find that when a reaction is older and contained in younger species, the reaction is more likely to be essential. Such correlations of essentiality with the ages of reactions and species may be attributable to the evolution of cellular metabolism, in which alternative pathways are recruited to ensure the stability of important reactions to various degrees across species.