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 (2023)
CYPArm2 is a CYP450 monooxygenase with protoilludene 13‐hydroxylase activity involved in the biosynthesis of armillyl orsellinate‐type sesquiterpenoids.
In: ChemBioChem, 24 (14)
doi: 10.1002/cbic.202300179
Article, Bibliographie

This is the latest version of this item.

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.

Item Type:

Article

Erschienen:

2023

Creators:

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

Type of entry:

Bibliographie

Title:

CYPArm2 is a CYP450 monooxygenase with protoilludene 13‐hydroxylase activity involved in the biosynthesis of armillyl orsellinate‐type sesquiterpenoids

Language:

English

Date:

2023

Place of Publication:

Weinheim

Publisher:

Wiley-VCH

Journal or Publication Title:

ChemBioChem

Volume of the journal:

Issue Number:

Collation:

8 Seiten

DOI:

10.1002/cbic.202300179

Corresponding Links:

TUprints secondary publication

Abstract:

Alternative Abstract:

Alternative abstract

Language

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.

English

Uncontrolled Keywords:

antimicrobial, Armillaria, cytochrome P450s, fungal sesquiterpenoids, melleolides

Identification Number:

Artikel-ID: e202300179

Classification DDC:

500 Science and mathematics > 540 Chemistry
500 Science and mathematics > 570 Life sciences, biology

Divisions:

07 Department of Chemistry
07 Department of Chemistry > Clemens-Schöpf-Institut

Date Deposited:

12 Feb 2024 07:54

Last Modified: