Dehydrobutyrine

Dehydrobutyrine, abbreviated Dhb, is a non-proteinogenic amino acid that appears as an α,β-unsaturated residue in certain ribosomally synthesized and post-translationally modified peptides (RiPPs), most notably lantibiotics. It arises by dehydration of threonine residues in a precursor peptide during maturation, yielding an α,β-unsaturated amino acid.

Chemically, Dhb is the dehydrated form of threonine and is an α,β-unsaturated amino acid, with a carbon–carbon double bond between the alpha and beta carbons of the residue. The double bond introduces electrophilic character that can influence the conformation and reactivity of the peptide. In many lantibiotics, the presence of Dhb (along with dehydroalanine residues) is a hallmark of the maturation process.

In lantibiotics and related lanthipeptides, Dhb residues commonly participate in intramolecular crosslinking with cysteine thiols to form thioether bridges, such as lanthionine and methyllanthionine rings. These crosslinks stabilize compact, rigid structures that contribute to the antimicrobial activity and thermal stability of the mature peptide.

Biosynthesis involves dedicated dehydration enzymes, typically LanB or LanM, which convert Ser and Thr residues to Dha and Dhb, respectively. The modified residues are then subjected to cyclization by LanC to install the characteristic thioether rings. The distribution and pattern of Dhb and related residues influence the spectrum of activity and the three-dimensional architecture of the final lantibiotic.

Dhb is primarily of biological interest as a structural and reactive feature of lantibiotics, illustrating how post-translational modification expands the chemical repertoire of natural peptides.