2. Academic Validation
  3. Cacaoidin, First Member of the New Lanthidin RiPP Family

Cacaoidin, First Member of the New Lanthidin RiPP Family

  • Angew Chem Int Ed Engl. 2020 Jul 27;59(31):12654-12658. doi: 10.1002/anie.202005187.
Francisco Javier Ortiz-López 1,  Daniel Carretero-Molina 1,  Marina Sánchez-Hidalgo 1,  Jesús Martín 1,  Ignacio González 1,  Fernando Román-Hurtado 1,  Mercedes de la Cruz 1,  Sergio García-Fernández 2,  Fernando Reyes 1,  Julia Patricia Deisinger 3 4,  Anna Müller 3,  Tanja Schneider 3 4,  Olga Genilloud 1
Affiliations

Affiliations

  • 1 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Avenida del Conocimiento, 34. Parque Tecnológico de Ciencias de la Salud, 18016 Armilla, Granada, Spain.
  • 2 Hospital Universitario, Ramón y Cajal. Ctra. de Colmenar Viejo, km. 9,100, 28034, Madrid, Spain.
  • 3 Institute for Pharmaceutical Microbiology, University Clinic Bonn, University of Bonn, Meckenheimer Allee 168, 53115, Bonn, Germany.
  • 4 DZIF, German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany.
PMID: 32407589 DOI: 10.1002/anie.202005187
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.

Keywords

RiPP family; lanthidin; lantibiotic; natural products; tyrosine-O-glycosylation.

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