Promiscuity of lanthipeptide enzymes: new challenges and applications

Lanthipeptides are a group of peptides synthesized by ribosomes that undergo post-translational modifications and have significant potential for medical and biotechnological applications. Various bacterial strains produce these peptides, and their synthesis involves the structural modification of precursor compounds through specialized enzymes present within a biosynthetic gene cluster (BGC) of the producing organisms. These enzymes are particularly notable for their capacity to modify non-cognate substrates, allowing for the installation of lanthionine rings on precursor peptides and enabling further modifications, such as methylation, reduction, and oxidation, to enhance the biological properties of specific peptides. The inherent flexibility of lanthipeptide enzymes-an important characteristic of this class of proteins-can be utilized to create peptides with improved bioactive and physicochemical properties. This review synthesizes recent advances in the application of promiscuous enzymes for the synthesis of bioactive peptides, emphasizing the diverse classes identified to date.