Nocathioamides, Uncovered by a Tunable Metabologenomic Approach, Define a Novel Class of Chimeric Lanthipeptides

The increasing number of available genomes, in combination with advanced genome mining techniques, unveiled a plethora of biosynthetic gene clusters (BGCs) coding for ribosomally synthesized and post‐translationally modified peptides (RiPPs). The products of these BGCs often represent an enormous re...

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Veröffentlicht in:Angewandte Chemie International Edition 2021-07, Vol.60 (30), p.16472-16479
Hauptverfasser: Saad, Hamada, Aziz, Saefuddin, Gehringer, Matthias, Kramer, Markus, Straetener, Jan, Berscheid, Anne, Brötz‐Oesterhelt, Heike, Gross, Harald
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container_issue 30
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container_title Angewandte Chemie International Edition
container_volume 60
creator Saad, Hamada
Aziz, Saefuddin
Gehringer, Matthias
Kramer, Markus
Straetener, Jan
Berscheid, Anne
Brötz‐Oesterhelt, Heike
Gross, Harald
description The increasing number of available genomes, in combination with advanced genome mining techniques, unveiled a plethora of biosynthetic gene clusters (BGCs) coding for ribosomally synthesized and post‐translationally modified peptides (RiPPs). The products of these BGCs often represent an enormous resource for new and bioactive compounds, but frequently, they cannot be readily isolated and remain cryptic. Here, we describe a tunable metabologenomic approach that recruits a synergism of bioinformatics in tandem with isotope‐ and NMR‐guided platform to identify the product of an orphan RiPP gene cluster in the genomes of Nocardia terpenica IFM 0406 and 0706T. The application of this tactic resulted in the discovery of nocathioamides family as a founder of a new class of chimeric lanthipeptides I. Chimeric Lanthipeptides: Employing a tunable metabologenomic approach, nocathioamides A–C were isolated and elucidated. They inaugurate a new RiPP family, characterized by a unique and hyper degree of modifications, including an intramolecular imide bridge.
doi_str_mv 10.1002/anie.202102571
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source Wiley Online Library All Journals
subjects Bioactive compounds
Bioinformatics
chimeric lanthipeptide
Gene clusters
Genomes
macrocyclic imide
metabologenomic approach
NMR
Nocardia terpenica
Nuclear magnetic resonance
Peptides
RiPPs
Synergism
title Nocathioamides, Uncovered by a Tunable Metabologenomic Approach, Define a Novel Class of Chimeric Lanthipeptides
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