AUTHOR=Lagedroste Marcel , Reiners Jens , Knospe C. Vivien , Smits Sander H. J. , Schmitt Lutz TITLE=A Structural View on the Maturation of Lanthipeptides JOURNAL=Frontiers in Microbiology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01183 DOI=10.3389/fmicb.2020.01183 ISSN=1664-302X ABSTRACT=

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, which display diverse bioactivities (e.g., antifungal, antimicrobial, and antiviral). One characteristic of these lanthipeptides is the presence of thioether bonds, which are termed (methyl-) lanthionine rings. These modifications are installed by corresponding modification enzymes in a two-step modality. First, serine and threonine residues are dehydrated followed by a subsequent catalyzed cyclization reaction, in which the dehydrated serine and threonine residues are undergoing a Michael-type addition with cysteine residues. The dedicated enzymes are encoded by one or two genes and the classification of lanthipeptides is pending on this. The modification steps form the basis of distinguishing the different classes of lanthipeptides and furthermore reflect also important mechanistic differences. Here, we will summarize recent insights into the mechanisms and the structures of the participating enzymes, focusing on the two core modification steps – dehydration and cyclization.