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CYPArm2 is a CYP450 Monooxygenase with Protoilludene 13‐Hydroxylase Activity Involved in the Biosynthesis of Armillyl Orsellinate‐Type Sesquiterpenoids

McElroy, Christopher ; Engels, Benedikt ; Meusinger, Reinhard ; Jennewein, Stefan (2024)
CYPArm2 is a CYP450 Monooxygenase with Protoilludene 13‐Hydroxylase Activity Involved in the Biosynthesis of Armillyl Orsellinate‐Type Sesquiterpenoids.
In: ChemBioChem, 2023, 24 (14)
doi: 10.26083/tuprints-00024657
Artikel, Zweitveröffentlichung, Verlagsversion

Es ist eine neuere Version dieses Eintrags verfügbar.

URL / URN: https://tuprints.ulb.tu-darmstadt.de/24657

Kurzbeschreibung (Abstract)

The melleolides are a family of structurally and functionally diverse sesquiterpenoids with potential applications as fungicides, antimicrobials, and cancer therapeutics. The initial and terminal steps of the biosynthesis pathway in Armillaria spp. have been characterized, but the intermediate steps are unclear. Biosynthetic gene clusters in A. mellea and A. gallica were shown to encode a terpene cyclase, a polyketide synthase, and four CYP450 monooxygenases. We have characterized CYPArm3, which is responsible for the hydroxylation of Δ‐6‐protoilludene, but the functions of the other CYP450s remain to be determined. Here we describe CYPArm2, which accepts Δ‐6‐protoilludene and 8α‐hydroxy‐6‐protoilludene as substrates. To investigate the products in more detail, we generated recombinant Saccharomyces cerevisiae strains overexpressing CYPArm2 in combination with the previously characterized protoilludene synthase and 8α‐hydroxylase. Using this total biosynthesis approach, sufficient quantities of product were obtained for NMR spectroscopy. This allowed the identification of 8α,13‐dihydroxy‐protoilludene, confirming that CYPArm2 is a protoilludene 13‐hydroxylase.

Typ des Eintrags:

Artikel

Erschienen:

2024

Autor(en):

McElroy, Christopher ; Engels, Benedikt ; Meusinger, Reinhard ; Jennewein, Stefan

Art des Eintrags:

Zweitveröffentlichung

Titel:

CYPArm2 is a CYP450 Monooxygenase with Protoilludene 13‐Hydroxylase Activity Involved in the Biosynthesis of Armillyl Orsellinate‐Type Sesquiterpenoids

Sprache:

Englisch

Publikationsjahr:

9 Februar 2024

Ort:

Darmstadt

Publikationsdatum der Erstveröffentlichung:

2023

Ort der Erstveröffentlichung:

Weinheim

Verlag:

Wiley-VCH

Titel der Zeitschrift, Zeitung oder Schriftenreihe:

ChemBioChem

Jahrgang/Volume einer Zeitschrift:

(Heft-)Nummer:

Kollation:

8 Seiten

DOI:

10.26083/tuprints-00024657

URL / URN:

https://tuprints.ulb.tu-darmstadt.de/24657

Zugehörige Links:

Verlags-DOI

Herkunft:

Zweitveröffentlichung DeepGreen

Kurzbeschreibung (Abstract):

Alternatives oder übersetztes Abstract:

Alternatives Abstract

Sprache

Melleolides and armillyl orsellinates are protoilludane-type aryl esters. Several of these compounds show potent antimicrobial and cytotoxic activities. Limited availability, however, hampers their pharmaceutical development. The elucidation of the biosynthetic pathway represents a prerequisite for the establishment of heterologous production systems. Here, we describe the identification of the protoilludene-13-hydroxylase.

Englisch

Freie Schlagworte:

antimicrobial, Armillaria, cytochrome P450s, fungal sesquiterpenoids, melleolides

ID-Nummer:

Artikel-ID: e202300179

Status:

Verlagsversion

URN:

urn:nbn:de:tuda-tuprints-246572

Sachgruppe der Dewey Dezimalklassifikatin (DDC):

500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie

Fachbereich(e)/-gebiet(e):