Nonproteinogenic

Nonproteinogenic refers to amino acids or amino acid–like residues that are not incorporated into proteins by the ribosome during translation. The standard, proteinogenic set typically comprises 20 canonical amino acids, although some organisms also use selenocysteine and pyrrolysine as special cases of genetic coding. Nonproteinogenic species include both L- and D- enantiomers and a wide range of derivatives that occur in metabolism, in secondary metabolites, or as post-translational modifications.

In nature, nonproteinogenic amino acids arise as metabolic intermediates (for example, GABA is derived from glutamate; ornithine and citrulline participate in the urea cycle) or as building blocks for specialized compounds. Some proteins also contain post-translationally modified residues, such as hydroxyproline in collagen, which expand structural diversity without changing the encoded sequence. D-amino acids are found in certain bacterial cell walls and rarely in proteins themselves.

Nonproteinogenic amino acids are important in research and biotechnology. They are used as probes and precursors in drug development, as labeling or stabilizing agents, and as components of nonribosomal peptides and other natural products. In protein engineering, genetic code expansion techniques introduce specific nonproteinogenic amino acids into proteins by engineered tRNA-synthetase pairs, enabling new chemical functionalities and applications.