title: Origins of specificity and promiscuity in metabolic networks.
abstract: How enzymes have evolved to their present form 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.
authors: Institute of Systems and Synthetic Biology, University of Evry, 91030 Evry, France.
authors: Pablo
authors: P
authors: Carbonell
authors: UMR 7138 Systématique Adaptation Evolution, Département Systématique et Evolution, Muséum National d'Histoire Naturelle, 75005 Paris, France.
authors: Guillaume
authors: G
authors: Lecointre
authors: Institute of Systems and Synthetic Biology, University of Evry, 91030 Evry, France. Electronic address: jean-loup.faulon@issb.genopole.fr.
authors: Jean-Loup
authors: JL
authors: Faulon
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D002384:Catalysis; D019295:Computational Biology / Q000379:methods; D003201:Computers; D004798:Enzymes / Q000737:chemistry; D019143:Evolution, Molecular; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways; D015233:Models, Statistical; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012984:Software; D013379:Substrate Specificity
chemical_list: D004798:Enzymes