title: The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture.
abstract: Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures. An analysis of newly discovered functions showed enzymatic diversification occurred early, during the onset of the modern protein world. Most importantly, phylogenetic reconstruction exercises and other evidence suggest strongly that metabolism originated in enzymes with the P-loop hydrolase fold in nucleotide metabolism, probably in pathways linked to the purine metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient biochemistry or prebiotic chemistry was related to the synthesis of nucleotides for the RNA world.
authors.affiliation: Departments of Crop Sciences and Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. gca@uiuc.edu
authors.forename: Gustavo
authors.initials: G
authors.lastname: Caetano-Anollés
authors.forename: Hee Shin
authors.initials: HS
authors.lastname: Kim
authors.forename: Jay E
authors.initials: JE
authors.lastname: Mittenthal
mesh_terms: D019143:Evolution, Molecular; D023281:Genomics; D053858:Metabolic Networks and Pathways; D009711:Nucleotides / Q000235:genetics; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D009711:Nucleotides; D011506:Proteins