Origins of Specificity and Promiscuity in Metabolic Networks

Pablo Carbonell, Guillaume Lecointre, Jean-Loup Faulon
2011 Journal of Biological Chemistry  
How enzymes evolved to their present form is linked to how extant metabolic pathways emerged. Results: Chemical diversity of reactions parallels enzyme phylogenetic diversity across the tree of life. Conclusion: Enzyme promiscuity plays a prominent role in the evolution of metabolic networks. Significance: Learning about the mechanisms of enzyme evolution might assist us with the identification of primeval catalytic functions and minimal metabolism. How enzymes have evolved to their present
more » ... is linked to the question of how pathways emerged and evolved into extant metabolic networks. To investigate this mechanism, we have explored the chemical diversity present in a largely unbiased data set of catalytic reactions processed by modern enzymes across the tree of life. In order to get a quantitative estimate of enzyme chemical diversity, we measure enzyme multispecificity or promiscuity using the reaction molecular signatures. Our main finding is that reactions that are catalyzed by a highly specific enzyme are shared by poorly divergent species, suggesting a later emergence of this function during evolution. In contrast, reactions that are catalyzed by highly promiscuous enzymes are more likely to appear uniformly distributed across species in the tree of life. From a functional point of view, promiscuous enzymes are mainly involved in amino acid and lipid metabolisms, which might be associated with the earliest form of biochemical reactions. In this way, results presented in this paper might assist us with the identification of primeval promiscuous catalytic functions contributing to life's minimal metabolism. Recent phylogenetic studies of cellular metabolism suggest a core set of highly conserved enzymes involved in amino acid, energy, carbohydrate, and lipid metabolism, which is likely to be associated with the ancestral form of the extant metabolic network (1, 2). However, the essentiality of this core for life and the existence of a universally essential minimal gene set are currently under debate, because essential genes show a diverse overall organization across multiple organisms in metabolic maps (3). This diversity might be explained, in part, by the role that enzyme promiscuity plays, providing a common background level of metabolism to the organisms (4). Thus, how enzymes have evolved to their present form in organisms appears to be linked to the question of how metabolic pathways emerged and configured extant metabolic networks (5). In fact, □ S The on-line version of this article (available at contains supplemental Tables S1 and S2 and Figs. S1-S10.
doi:10.1074/jbc.m111.274050 pmid:22052908 pmcid:PMC3243566 fatcat:c3sew5kimjarfkgfyqwmqsxxfu