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 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.

Genome mining reveals the evolutionary origin and biosynthetic potential of basidiomycete polyketide synthases.

Numerous polyketides are known from bacteria, plants, and fungi. However, only a few have been isolated from basidiomycetes. Large scale genome sequencing projects now help anticipate the capacity of basidiomycetes to synthesize polyketides.

Characterisation of the ArmA adenylation domain implies a more diverse secondary metabolism in the genus Armillaria.

The armA-gene, encoding a tridomain enzyme reminiscent of nonribosomal peptide synthetases, was identified in the genome of the basidiomycete Armillaria mellea. Heterologously expressed enzyme and the ATP-pyrophosphate exchange assay were used for the in vitro biochemical characterisation of the ArmA adenylation domain. l-leucine was the preferred substrate, while l-threonine, l-valine, l-alanine, and l-isoleucine were turned over at lower rates (83 %, 62 %, 56 %, and 44 %, respectively).

Structure and cytotoxicity of arnamial and related fungal sesquiterpene aryl esters.

We report on the structure elucidation of arnamial, a new Delta(2,4)-protoilludane everninate ester from the fungus Armillaria mellea, and on the apoptotic activity of arnamial as well as the cytotoxic activity of structurally related compounds on selected human cancer cells. Arnamial showed cytotoxicity against Jurkat T cells, MCF-7 breast adenocarcinoma, CCRF-CEM lymphoblastic leukemia, and HCT-116 colorectal carcinoma cells at IC50 = 3.9, 15.

In vivo and in vitro production options for fungal secondary metabolites.

Microbial natural products, among them a vast diversity of fungal origin, represent a major source for new drug candidates. Focusing on fungal metabolites, our review covers recent advances in the field of biotransformation, heterologous expression, in vivo production approaches, genomics, and the metabolism of unexplored fungal groups as options to generate and identify new compounds or optimize known ones.

Processing sites involved in intron splicing of Armillaria natural product genes.

We analysed the structure of four genes whose transcriptional products are likely to be involved in the small molecule metabolism of the homobasidiomycete Armillaria mellea with the aim of verifying splice sites. To this end we experimentally validated in silico predicted intron/exon junctions for accuracy. Based on 78 verified junctions, a consensus for donor and acceptor sites in Armillaria is presented, along with experimental evidence for non-canonical splice sites, introns with alternative donor or acceptor junctions, and allele-selective splicing.

Fungal genetics, genomics, and secondary metabolites in pharmaceutical sciences.

Filamentous fungi produce a plethora of bioactive natural products. These metabolites display a broad range of useful activities for pharmaceutical purposes, exemplified best by the antibiotic penicillin. Yet, many more have been isolated, characterised, and tested, and some have made their way in clinical trials and into pharmaceutical practice.