From Metabolism to Mutation: The Multifaceted Roles of Deaminases in Biological Systems

Deaminases are versatile enzymes present across all domains of life, playing pivotal roles in metabolism, cellular and organ development, heme and vitamin biosynthesis, toxin modulation, antibiotic degradation, the modification of nucleobases, and the mutation of RNA and DNA. This review explores the structural and functional diversity of deaminases, highlighting their mechanisms and evolutionary adaptations. Deaminases catalyze the removal of amine groups, typically using metal cations and proton shuttles to facilitate hydroxyl group incorporation, with some reactions employing pyridoxal 5'-phosphate (PLP) as a cofactor. The review categorizes deaminases based on their substrates, including porphobilinogen, amino sugars, amino acids, and nucleobases. Particular emphasis is placed on nucleobase deaminases due to their roles in RNA/DNA editing and mutagenesis which have significant implications in immune response, cancer progression, and viral defense mechanisms. Structural insights reveal the diverse evolutionary pathways of these enzymes, from simple single-domain forms to complex multi-domain configurations that enable processive deamination of polynucleotides. Through a comprehensive analysis of deaminase families—PBGD, sugar deaminases, amino acid deaminases, and nucleobase deaminases—this review underscores their biological significance and potential applications in agriculture, medicine, and biotechnology, providing a foundational understanding for future research.