Natural Occurring and Engineered Enzymes for Peptide Ligation and Cyclization

The renaissance of peptides as prospective therapeutics has fostered the development of novel strategies for their synthesis and modification. In this context, besides the developmentofnewchemicalpeptideligationapproaches,especiallytheuseofenzymes as a versatile tool has gained increased attention. Nowadays, due to their inherent properties such as excellent regio- and chemoselectivity, enzymes represent invaluable instruments in both academic and industrial laboratories. This mini-review focuses on natural- and engineered peptide ligases that can form a new peptide (amide) bond between the C-terminal carboxy and N-terminal amino group of a peptide and/or protein. The pro’s and cons of several enzyme classes such as Sortases, Asparaginyl Endoproteases, Trypsin relatedenzymesand as a centralfocus subtilisin-derived variants are summarized. Most recent developments with regards to ligation and cyclization are highlighted