摘要
Hydrolytic enzymes, such as lactamases or hydantoinases, can be valuably applied to convert lactams (cyclic amides) and cyclic imides into optically pure compounds, for example, d- or l- amino acids, and to resolve racemic mixtures, such as Vince lactams. The chiral building blocks can be utilized to produce biologically active peptides, pesticides, sweeteners, and antibiotics, such as semisynthetic penicillins or cephalosporins. Furthermore, these compounds find application as feed and food additives and constitute useful intermediates for cosmetics, pharmaceuticals, or agrochemicals. Beyond their application in chemical synthesis, cyclic amide and imide hydrolyzing enzymes hold promise in the recovery of materials containing polyamides or in the bioremediation of antibiotics and herbicides. Today, lactam and cyclic imide hydrolyzing biocatalysts mainly originate from enzyme families associated with two distinct structural archetypes: (a) α/β-hydrolases (e.g., lipases) and (b) metal-dependent amidohydrolases (e.g., dihydropyrimidinases/hydantoinases). Beyond these well-explored sources, nature offers an additional wealth of mechanistically, catalytically, and structurally distinct enzymes for lactam and cyclic imide hydrolysis, including serine and metallo-β-lactamases, allantoinases, 5-oxoprolinases, and members of the amidase signature family. To facilitate the discovery of suitable biocatalysts for such types of hydrolysis reactions, we provide a comprehensive overview of application examples, as well as functional annotations (EC identifiers) and structural architectures (CATH identifiers), of the currently known biocatalytic toolbox. In addition, a protein sequence database containing all relevant biocatalyst superfamilies for cyclic amide and imide hydrolysis has been created (https://github.com/ccbiozhaw/CyclAmidImid).