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

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

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.

• Jezik: Angleški jezik
• Ključne besede: myxobacteria, secondary metabolites, biarylitide, natural product discovery, RiPPs, genome mining, Myxarylin
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: VF - Veterinarska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Datum objave: 10.12.2021
• Leto izida: 2021
• Št. strani: 17 str.
• Številčenje: Vol. 26, no. 24, art. 7483
• PID: 20.500.12556/RUL-134001
• UDK: 575
• ISSN pri članku: 1420-3049
• DOI: 10.3390/molecules26247483
• COBISS.SI-ID: 90433027
• Datum objave v RUL: 21.12.2021

Gradivo je del revije

• Naslov: Molecules
• Skrajšan naslov: Molecules
• Založnik: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 21.12.2021

Projekti

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: 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