This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: The enzymes found in modern organisms are complex proteins, often with multiple folded substructures and specialized catalytic sites. Proteins are encoded by genes.
Tracing the history of enzymes across all living organisms through gene comparisons leads to the last universal common ancestor (LUCA), a hypothetical organism that existed around 4 billion years ago and is believed to be the ancestor of life forms on Earth. However, even LUCA's proteins must have been complex enough to run the core machinery of a living cell. Because comparative analyses cannot explain how proteins evolved before LUCA emerged, alternative approaches are needed to reveal the earliest enzymes.
One possible approach is to examine the evolution of enzymes that catalyze metabolic reactions, including the breakdown of molecules in the cell to extract energy and the synthesis of complex metabolites. Metabolic reactions are layered, meaning the end product of one reaction becomes the raw material for another, resulting in a complex web. "Emphasizing the layered structure of metabolism has produced significant insights into the chemistry of primitive metabolic systems and the environment of the earliest life.
Here, we use this approach to study the evolution of the first enzymes," notes Dr. Longo, specially appointed associate professor at the Earth-Life Science Institute (ELSI), Institute of Science Tokyo (Science Tokyo), Japan. Longo, along with Specially Appointed Associate Professor Harrison B.
Smith and doctoral student Tatsuya Corlett, both from ELSI at Science Tokyo, led an international research effort to reconstruct the history of enzymes based on the layers of metabolism. Their findings are published in Proceedings of the National Academy of Sciences. Longo's team first turned to large databases of metabolic reactions and protein structures.
Using a model of metabolic evolution based on biochemical data from the Kyoto Encyclopedia of Genes and Genomes, they identified 4,294 metabolites and 7,678 reactions mediated by 4,331 enzymes and their variants. From the Evolutionary Classification of Domains database, they identified 396 metabolic protein folds, each of which adopts one of six structure types. With these data as the foundation, the team developed a model of metabolic layering that began with simple molecules believed to have existed on Earth before LUCA.
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