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.