Bacterial β ‐Aminopeptidases: Structural Insights and Applications for Biocatalysis

Abstract β ‐Aminopeptidases comprise a class of enzymes with functional and structural similarities. All members of the β ‐aminopeptidases described to date were isolated from bacterial sources. Uniquely, they catalyze the hydrolysis of β 3 ‐ and/or β 2 ‐amino acid residues from amides and peptides that are otherwise considered proteolytically stable. Due to this unusual reactivity with β ‐peptide substrates, β ‐aminopeptidases have potential to be used as biocatalysts for β ‐peptide synthesis and for the resolution of enantiomerically pure β ‐amino acids from racemic substrate mixtures. β ‐Aminopeptidases are formed from an inactive precursor by posttranslational autoproteolytic cleavage, exposing the catalytic nucleophile at the N‐terminus of the newly formed β ‐polypeptide chain. Such an activation step is a characteristic trait of enzymes of the N‐terminal nucleophile (Ntn) hydrolase superfamily. However, classical Ntn hydrolases and β ‐aminopeptidases differ by the fold of their catalytic cores and are hence likely to originate from distinct evolutionary ancestors. In this contribution, we review the existing literature on β ‐aminopeptidases, including biochemical and functional studies, as well as structural investigations that recently allowed insights into the catalytic mechanisms of precursor processing and β ‐peptide conversion.