2007/05/22 by Gustavo Caetano‐Anollés, Hee Shin Kim, Jay E. Mittenthal · 2 citations
Biochemistry, Genetics and Molecular Biology · Physics and Astronomy · #Protein Structure and Dynamics #Microbial Metabolic Engineering and Bioproduction #Origins and Evolution of Life
paper · pdf · doi:10.1073/pnas.0701214104
openalex publication_date 2007/05/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
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.