Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi

Abstract We gathered a collection of termite mutualistic strains from French Guiana to explore the metabolites of symbiotic microorganisms. Molecular networks reconstructed from a metabolomic analysis using LC–ESI–MS/MS methodology led us to identify two families of chlorinated polyketides, i.e., az...

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Main Authors: Téo Hebra, Nicolas Pollet, David Touboul, Véronique Eparvier
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-22256-3
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author Téo Hebra
Nicolas Pollet
David Touboul
Véronique Eparvier
author_facet Téo Hebra
Nicolas Pollet
David Touboul
Véronique Eparvier
author_sort Téo Hebra
collection DOAJ
description Abstract We gathered a collection of termite mutualistic strains from French Guiana to explore the metabolites of symbiotic microorganisms. Molecular networks reconstructed from a metabolomic analysis using LC–ESI–MS/MS methodology led us to identify two families of chlorinated polyketides, i.e., azaphilones from Penicillium sclerotiorum and ilicicolins from Neonectria discophora. To define the biosynthetic pathways related to these two types of scaffolds, we used a whole genome sequencing approach followed by hybrid assembly from short and long reads. We found two biosynthetic gene clusters, including two FAD-dependent halogenases. To exploit the enzymatic promiscuity of the two identified FAD halogenases, we sought to biosynthesize novel halogenated metabolites. An OSMAC strategy was used and resulted in the production of brominated analogs of ilicicolins and azaphilones as well as iodinated analogs of azaphilones.
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spelling doaj.art-4aaf70c5763347beba459180151d56832022-12-22T04:31:55ZengNature PortfolioScientific Reports2045-23222022-10-0112111210.1038/s41598-022-22256-3Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungiTéo Hebra0Nicolas Pollet1David Touboul2Véronique Eparvier3Université Paris-Saclay, CNRS, Institut de Chimie Des Substances Naturelles, UPR 2301Université Paris-Saclay, CNRS, IRD, Évolution Génomes Comportement & ÉcologieUniversité Paris-Saclay, CNRS, Institut de Chimie Des Substances Naturelles, UPR 2301Université Paris-Saclay, CNRS, Institut de Chimie Des Substances Naturelles, UPR 2301Abstract We gathered a collection of termite mutualistic strains from French Guiana to explore the metabolites of symbiotic microorganisms. Molecular networks reconstructed from a metabolomic analysis using LC–ESI–MS/MS methodology led us to identify two families of chlorinated polyketides, i.e., azaphilones from Penicillium sclerotiorum and ilicicolins from Neonectria discophora. To define the biosynthetic pathways related to these two types of scaffolds, we used a whole genome sequencing approach followed by hybrid assembly from short and long reads. We found two biosynthetic gene clusters, including two FAD-dependent halogenases. To exploit the enzymatic promiscuity of the two identified FAD halogenases, we sought to biosynthesize novel halogenated metabolites. An OSMAC strategy was used and resulted in the production of brominated analogs of ilicicolins and azaphilones as well as iodinated analogs of azaphilones.https://doi.org/10.1038/s41598-022-22256-3
spellingShingle Téo Hebra
Nicolas Pollet
David Touboul
Véronique Eparvier
Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi
Scientific Reports
title Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi
title_full Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi
title_fullStr Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi
title_full_unstemmed Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi
title_short Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi
title_sort combining osmac metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic fungi
url https://doi.org/10.1038/s41598-022-22256-3
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