Engels, Benedikt ; Heinig, Uwe ; McElroy, Christopher ; Meusinger, Reinhard ; Grothe, Torsten ; Stadler, Marc ; Jennewein, Stefan (2024)
Isolation of a gene cluster from Armillaria gallica for the synthesis of armillyl orsellinate–type sesquiterpenoids.
In: Applied Microbiology and Biotechnology, 2021, 105 (1)
doi: 10.26083/tuprints-00023906
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Melleolides 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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Engels, Benedikt ; Heinig, Uwe ; McElroy, Christopher ; Meusinger, Reinhard ; Grothe, Torsten ; Stadler, Marc ; Jennewein, Stefan |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Isolation of a gene cluster from Armillaria gallica for the synthesis of armillyl orsellinate–type sesquiterpenoids |
| Sprache: | Englisch |
| Publikationsjahr: | 30 April 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | Januar 2021 |
| Ort der Erstveröffentlichung: | Berlin ; Heidelberg ; New York |
| Verlag: | Springer |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Applied Microbiology and Biotechnology |
| Jahrgang/Volume einer Zeitschrift: | 105 |
| (Heft-)Nummer: | 1 |
| DOI: | 10.26083/tuprints-00023906 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/23906 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Melleolides 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. |
| Freie Schlagworte: | Antibiotics, Chemotherapy, Drug discovery, Melleolide, Natural product biosynthesis, Terpenoid |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-239066 |
| Zusätzliche Informationen: | 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. |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 30 Apr 2024 11:19 |
| Letzte Änderung: | 02 Mai 2024 07:39 |
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| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
- Isolation of a gene cluster from Armillaria gallica for the synthesis of armillyl orsellinate–type sesquiterpenoids. (deposited 30 Apr 2024 11:19) [Gegenwärtig angezeigt]
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