Correlation-enhanced viable core in metabolic networks

Abstract

Cellular ingredient concentrations can be stabilized by adjusting generation and consumption rates through multiple pathways. To explore the portion of cellular metabolism equipped with multiple pathways, we categorize individual metabolic reactions and compounds as viable or inviable: A compound is viable if processed by two or more reactions, and a reaction is viable if all of its substrates and products are viable. Using this classification, we identify the maximal subnetwork of viable nodes, referred to as the viable core, in bipartite metabolic networks across thousands of species. The obtained viable cores are remarkably larger than those in degree-preserving randomized networks, while their broad degree distributions commonly enable the viable cores to shrink gradually as reaction nodes are deleted. We demonstrate by investigating the viable cores and the branching ratios of inviable nodes in the pruning process for artificial correlated networks that the positive degree–degree correlations of the empirical networks may underlie the enlarged viable cores compared to the randomized networks. By investigating the relation between degree and cross-species frequency of metabolic compounds and reactions, we elucidate the evolutionary origin of the correlations. Our study unveils the principle of metabolic resource allocation and its evolutionary mechanism, potentially useful for pharmaceutical applications. © 2024 Elsevier Ltd