20.500.12556/RUL-134001 Genome-guided discovery of the first myxobacterial biarylitide Myxarylin reveals distinct C–N biaryl crosslinking in RiPP biosynthesis 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. myxobacteria secondary metabolites biarylitide natural product discovery RiPPs genome mining Myxarylin true false true Angleški jezik Ni določen Članek v reviji 2021-12-21 16:38:59 2021-12-21 16:39:00 2022-09-13 03:52:55 0000-00-00 00:00:00 2021 0 0 17 str. no. 24, art. 7483 Vol. 26 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2021-12-10 575 1420-3049 10.3390/molecules26247483 90433027 RAZ_Hug_Joachim_J._2021.pdf RAZ_Hug_Joachim_J._2021.pdf 1 4A24506D74E1C2CCBF5E64DD31F44FE2 1bf01aee3f623768b5f3e77431046ce045ea2821f38d7be84d6ce57ec5d6f4e8 ffb48aa2-6275-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152321 https://www.mdpi.com/1420-3049/26/24/7483 Odprti dostop 1 fad7c399-6273-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152320 Veterinarska fakulteta 0 0 0