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A Self‐Sacrificing N ‐Methyltransferase Is the Precursor of the Fungal Natural Product Omphalotin
Author(s) -
Ramm Sascha,
Krawczyk Bartlomiej,
Mühlenweg Agnes,
Poch Annette,
Mösker Eva,
Süssmuth Roderich D.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201703488
Subject(s) - nonribosomal peptide , biosynthesis , natural product , peptide , methyltransferase , biochemistry , peptide biosynthesis , enzyme , gene , genome , chemistry , protease , biology , computational biology , methylation , rna , ribosome
Research on ribosomally synthesized and posttranslationally modified peptides (RiPPs) has led to an increasing understanding of biosynthetic mechanisms, mostly drawn from bacterial examples. In contrast, reports on RiPPs from fungal producers, apart from the amanitins and phalloidins, are still scarce. The fungal cyclopeptide omphalotin A carries multiple N‐methylations on the peptide backbone, a modification previously known only from nonribosomal peptides. Mining the genome of the omphalotin‐producing fungus for a precursor peptide led to the identification of two biosynthesis genes, one encoding a methyltransferase OphMA that catalyzes the automethylation of its C‐terminus, which is then released and cyclized by the protease OphP. Our findings suggest a novel biosynthesis mechanism for a RiPP in which a modifying enzyme bears its own precursor peptide.