Elucidation of the Bridging Pattern of the Lantibiotic Pseudomycoicidin. (7th December 2022)

• Record Type: Journal Article
• Authors: Janssen, Kathrin; Krasenbrink, Julia; Strangfeld, Sarina; Kroheck, Sarah; Josten, Michaele; Engeser, Marianne; Bierbaum, Gabriele
• Is Part Of: Chembiochem. Volume 24:Number 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-07
• Subjects: antimicrobials -- lantibiotics -- MALDI-TOF-MS -- pseudomycoicidin -- ring structures; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200540
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Lantibiotics are post‐translationally modified antibiotic peptides with lanthionine thioether bridges that represent potential alternatives to conventional antibiotics. The lantibiotic pseudomycoicidin is produced by Bacillus pseudomycoides DSM 12442 and is effective against many Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus . While prior work demonstrated that pseudomycoicidin possesses one disulfide bridge and four thioether bridges, the ring topology has so far remained unclear. Here, we analyzed several pseudomycoicidin analogues that are affected in ring formation via MALDI‐TOF‐MS and tandem mass spectrometry with regard to their dehydration and fragmentation patterns, respectively. As a result, we propose a bridging pattern involving Thr8 and Cys13, Thr10 and Cys16, Ser18 and Cys21, and Ser20 and Cys26, thus, forming two double ring systems. Additionally, we localized the disulfide bridge to connect Cys3 and Cys7 and, therefore, fully elucidated the bridging pattern of pseudomycoicidin. Abstract : The bridging pattern of the lantibiotic pseudomycoicidin, a (methyl‐)lanthionine‐containing antibiotic peptide that is produced by Bacillus pseudomycoides is elucidated here. An alanine scan and MALDI TOF MS of variant peptides showed that the peptide is characterized by a compact structure with two double ring systems, one disulfide bridge, and a possible conserved lipid II binding motif.