Josué Fabián Díaz Aguilar, Mario Israel Hernández Alva
The predominance of L-amino acids in biological systems has long been considered a defining feature of life. However, accumulating evidence over the past decades has demonstrated that D-amino acids are not merely biochemical anomalies, but biologically relevant molecules with diverse and essential functions across all domains of life. This review summarizes current knowledge on the distribution, biosynthesis, metabolism, and physiological roles of D-amino acids, highlighting their significance in microbial, animal, and evolutionary contexts. In bacteria, D-amino acids such as D-alanine and D-glutamate are integral components of peptidoglycan, contributing to cell wall integrity and resistance to proteolytic degradation. Beyond structural roles, several noncanonical D-amino acids act as signaling molecules to biofilm formation and microbial community dynamics. In eukaryotes, particularly in mammals, D-serine and D-aspartate have emerged as key neuromodulators involved in synaptic plasticity, neurodevelopment, and endocrine regulation, with growing implications in neurological and psychiatric disorders. Furthermore, the coexistence of functional D-amino acids with the largely L-based proteome raises fundamental questions about the origin and maintenance of biological homochirality. Mechanisms such as stereospecific aminoacyl-tRNA synthetases and D-aminoacyl-tRNA deacylases actively preserve proteomic homochirality while allowing selective utilization of D-amino acids in specialized pathways. Overall, D-amino acids represent a crucial yet historically underappreciated dimension of biological chemistry, with implications ranging from microbial physiology to neuroscience and the origin of life.