title: Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes.
abstract: Lanthipeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that display a wide variety of biological activities, from antimicrobial to antiallodynic. Lanthipeptides that display antimicrobial activity are called lantibiotics. The post-translational modification reactions of lanthipeptides include dehydration of Ser and Thr residues to dehydroalanine and dehydrobutyrine, a transformation that is carried out in three unique ways in different classes of lanthipeptides. In a cyclization process, Cys residues then attack the dehydrated residues to generate the lanthionine and methyllanthionine thioether cross-linked amino acids from which lanthipeptides derive their name. The resulting polycyclic peptides have constrained conformations that confer their biological activities. After installation of the characteristic thioether cross-links, tailoring enzymes introduce additional post-translational modifications that are unique to each lanthipeptide and that fine-tune their activities and/or stability. This review focuses on studies published over the past decade that have provided much insight into the mechanisms of the enzymes that carry out the post-translational modifications.
authors.affiliation: Howard Hughes Medical Institute and Department of Chemistry, ‡Department of Biochemistry, and §Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Repka
authors.affiliation: Howard Hughes Medical Institute and Department of Chemistry, ‡Department of Biochemistry, and §Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Chekan
authors.affiliation: Howard Hughes Medical Institute and Department of Chemistry, ‡Department of Biochemistry, and §Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Satish K
authors.identifier: http://orcid.org/0000-0003-1790-1334
authors.initials: SK
authors.lastname: Nair
authors.affiliation: Howard Hughes Medical Institute and Department of Chemistry, ‡Department of Biochemistry, and §Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Wilfred A
authors.identifier: http://orcid.org/0000-0002-5467-7071
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D001430:Bacteriocins / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D011499:Protein Processing, Post-Translational
chemical_list: D001430:Bacteriocins; D004798:Enzymes; D010455:Peptides