A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins

The basidiomycetous tree pathogen Armillaria mellea (honey mushroom) produces a large variety of structurally related antibiotically active and phytotoxic natural products, referred to as the melleolides. During their biosynthesis, some members of the melleolide family of compounds undergo monochlor...

Full description

Saved in:
Bibliographic Details
Published in:Applied and environmental microbiology 2016-02, Vol.82 (4), p.1196-1204
Main Authors: Wick, Jonas, Heine, Daniel, Lackner, Gerald, Misiek, Mathias, Tauber, James, Jagusch, Hans, Hertweck, Christian, Hoffmeister, Dirk
Format: Article
Language:English
Subjects:
Armillaria - enzymology
Armillaria - genetics
Armillaria - metabolism
Armillaria mellea
Ascomycetes
Basidiomycetes
Biosynthesis
Chlorine
E coli
Enzymes
Enzymology and Protein Engineering
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Gene Expression
Halogenation
Mushrooms
Mycotoxins - metabolism
Oxidoreductases - genetics
Oxidoreductases - metabolism
Phylogenetics
Sesquiterpenes - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The basidiomycetous tree pathogen Armillaria mellea (honey mushroom) produces a large variety of structurally related antibiotically active and phytotoxic natural products, referred to as the melleolides. During their biosynthesis, some members of the melleolide family of compounds undergo monochlorination of the aromatic moiety, whose biochemical and genetic basis was not known previously. This first study on basidiomycete halogenases presents the biochemical in vitro characterization of five flavin-dependent A. mellea enzymes (ArmH1 to ArmH5) that were heterologously produced in Escherichia coli. We demonstrate that all five enzymes transfer a single chlorine atom to the melleolide backbone. A 5-fold, secured biosynthetic step during natural product assembly is unprecedented. Typically, flavin-dependent halogenases are categorized into enzymes acting on free compounds as opposed to those requiring a carrier-protein-bound acceptor substrate. The enzymes characterized in this study clearly turned over free substrates. Phylogenetic clades of halogenases suggest that all fungal enzymes share an ancestor and reflect a clear divergence between ascomycetes and basidiomycetes.
ISSN:0099-2240
1098-5336
DOI:10.1128/AEM.03168-15