Show simple item record

dc.contributor.authorEngels, Benedikt
dc.contributor.authorHeinig, Uwe
dc.contributor.authorMcElroy, Christopher
dc.contributor.authorMeusinger, Reinhard
dc.contributor.authorGrothe, Torsten
dc.contributor.authorStadler, Marc
dc.contributor.authorJennewein, Stefan
dc.date.accessioned2020-12-10T13:46:13Z
dc.date.available2020-12-10T13:46:13Z
dc.date.issued2020-11-16
dc.identifier.citationAppl Microbiol Biotechnol. 2020 Nov 16. doi: 10.1007/s00253-020-11006-y. Epub ahead of print.en_US
dc.identifier.pmid33191459
dc.identifier.doi10.1007/s00253-020-11006-y
dc.identifier.urihttp://hdl.handle.net/10033/622645
dc.description.abstractMelleolides and armillyl orsellinates are protoilludene-type aryl esters that are synthesized exclusively by parasitic fungi of the globally distributed genus Armillaria (Agaricomycetes, Physalacriaceae). Several of these compounds show potent antimicrobial and cytotoxic activities, making them promising leads for the development of new antibiotics or drugs for the treatment of cancer. We recently cloned and characterized the Armillaria gallica gene Pro1 encoding protoilludene synthase, a sesquiterpene cyclase catalyzing the pathway-committing step to all protoilludene-type aryl esters. Fungal enzymes representing secondary metabolic pathways are sometimes encoded by gene clusters, so we hypothesized that the missing steps in the pathway to melleolides and armillyl orsellinates might be identified by cloning the genes surrounding Pro1. Here we report the isolation of an A. gallica gene cluster encoding protoilludene synthase and four cytochrome P450 monooxygenases. Heterologous expression and functional analysis resulted in the identification of protoilludene-8α-hydroxylase, which catalyzes the first committed step in the armillyl orsellinate pathway. This confirms that ∆-6-protoilludene is a precursor for the synthesis of both melleolides and armillyl orsellinates, but the two pathways already branch at the level of the first oxygenation step. Our results provide insight into the synthesis of these valuable natural products and pave the way for their production by metabolic engineering. KEY POINTS: • Protoilludene-type aryl esters are bioactive metabolites produced by Armillaria spp. • The pathway-committing step to these compounds is catalyzed by protoilludene synthase. • We characterized CYP-type enzymes in the cluster and identified novel intermediates.en_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAntibioticsen_US
dc.subjectChemotherapyen_US
dc.subjectDrug discoveryen_US
dc.subjectMelleolideen_US
dc.subjectNatural product biosynthesisen_US
dc.subjectTerpenoiden_US
dc.titleIsolation of a gene cluster from Armillaria gallica for the synthesis of armillyl orsellinate-type sesquiterpenoids.en_US
dc.typeArticleen_US
dc.identifier.eissn1432-0614
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalApplied microbiology and biotechnologyen_US
refterms.dateFOA2020-12-10T13:46:14Z
dc.source.journaltitleApplied microbiology and biotechnology
dc.source.countryGermany


Files in this item

Thumbnail
Name:
Engels et al.pdf
Size:
788.4Kb
Format:
PDF
Description:
Open Access publication

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International