Cacaoidin, First Member of the New Lanthidin RiPP Family. (15th June 2020)

• Record Type: Journal Article
• Authors: Ortiz‐López, Francisco Javier; Carretero‐Molina, Daniel; Sánchez‐Hidalgo, Marina; Martín, Jesús; González, Ignacio; Román‐Hurtado, Fernando; de la Cruz, Mercedes; García‐Fernández, Sergio; Reyes, Fernando; Deisinger, Julia Patricia; Müller, Anna; Schneider, Tanja; Genilloud, Olga
• Is Part Of: Angewandte Chemie. Volume 132:Number 31(2020)
• Page Start: 12754
• Page End: 12758
• Publication Date: 2020-06-15
• Subjects: lanthidin -- lantibiotic -- natural products -- RiPP family -- tyrosine-O-glycosylation; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202005187
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Lantibiotics are ribosomally synthesized and post‐translationally modified peptides (RiPPs) characterized by the presence of lanthionine or methyllanthionine rings and their antimicrobial activity. Cacaoidin, a novel glycosylated lantibiotic, was isolated from a Streptomyces cacaoi strain and fully characterized by NMR, mass spectrometry, chemical derivatization approaches and genome analysis. The new molecule combines outstanding structural features, such as a high number of d ‐amino acids, an uncommon glycosylated tyrosine residue and an unprecedented N, N‐dimethyl lanthionine. This latter feature places cacaoidin within a new RiPP family located between lanthipeptides and linaridins, here termed lanthidins. Cacaoidin displayed potent antibacterial activity against Gram‐positive pathogens including Clostridium difficile. The biosynthetic gene cluster showed low homology with those of other known lanthipeptides or linaridins, suggesting a new RiPP biosynthetic pathway. Abstract : Lanthidins : A novel glycosylated lantibiotic, cacaoidin, inaugurates a new RiPP family characterized by the co‐occurrence of lanthionine rings and N‐terminus dimethylation, structural features both restricted to the lanthipeptide and linaridin RiPP families, respectively. Cacaoidin combines both elements in an unprecedented N, N ‐dimethyl lanthionine system and exhibits a rare tyrosine‐ O ‐glycosylated residue.