Genome-guided discovery of the first myxobacterial biarylitide Myxarylin reveals distinct C–N biaryl crosslinking in RiPP biosynthesis

Hug, Joachim J. (author), Frank, Nicolas A. (author), Walt, Christine (author), Šenica, Petra (author), Panter, Fabian (author), Müller, Rolf (author)

Abstract Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse group of natural products. They feature a wide range of intriguing post-translational modifications, as exemplified by the biarylitides. These are a family of cyclic tripeptides found in Planomonospora, carrying a biaryl linkage between two aromatic amino acids. Recent genomic analyses revealed that the minimal biosynthetic prerequisite of biarylitide biosynthesis consists of only one ribosomally synthesized pentapeptide precursor as the substrate and a modifying cytochrome- P450-dependent enzyme. In silico analyses revealed that minimal biarylitide RiPP clusters are widespread among natural product producers across phylogenetic borders, including myxobacteria. We report here the genome-guided discovery of the first myxobacterial biarylitide MeYLH, termed Myxarylin, from Pyxidicoccus fallax An d48. Myxarylin was found to be an N-methylated tripeptide that surprisingly exhibits a C–N biaryl crosslink. In contrast to Myxarylin, previously isolated biarylitides are N-acetylated tripeptides that feature a C–C biaryl crosslink. Furthermore, the formation of Myxarylin was confirmed by the heterologous expression of the identified biosynthetic genes in Myxococcus xanthus DK1622. These findings expand the structural and biosynthetic scope of biarylitide-type RiPPs and emphasize the distinct biochemistry found in the myxobacterial realm.

• Language: English
• Keywords: myxobacteria, secondary metabolites, biarylitide, natural product discovery, RiPPs, genome mining, Myxarylin
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: VF - Veterinary Faculty
• Publication status: Published
• Publication version: Version of Record
• Publication date: 10.12.2021
• Year: 2021
• Number of pages: 17 str.
• Numbering: Vol. 26, no. 24, art. 7483
• PID: 20.500.12556/RUL-134001
• UDC: 575
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules26247483
• COBISS.SI-ID: 90433027
• Publication date in RUL: 21.12.2021

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 21.12.2021

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Research in Rolf Müller’s laboratory is funded by the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF) and the Deutsches Zentrum für Infektionsforschung Standort Hannover-Braunschweig