title: Chemical synthesis of the lantibiotic lacticin 481 reveals the importance of lanthionine stereochemistry.
abstract: Lantibiotics are a family of antibacterial peptide natural products characterized by the post-translational installation of the thioether-containing amino acids lanthionine and methyllanthionine. Until recently, only a single naturally occurring stereochemical configuration for each of these cross-links was known. The discovery of lantibiotics with alternative lanthionine and methyllanthionine stereochemistry has prompted an investigation of its importance to biological activity. Here, solid-supported chemical synthesis enabled the total synthesis of the lantibiotic lacticin 481 and analogues containing cross-links with non-native stereochemical configurations. Biological evaluation revealed that these alterations abolished the antibacterial activity in all of the analogues, revealing the critical importance of the enzymatically installed stereochemistry for the biological activity of lacticin 481.
authors.affiliation: Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Knerr
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001430:Bacteriocins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013294:Lactococcus lactis / Q000737:chemistry* / Q000187:drug effects; D008969:Molecular Sequence Data; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C082508:lacticin 481