Depicting the Chemical Diversity of Bioactive Meroterpenoids Produced by the Largest Organism on Earth

Abstract

In this investigation, we explored the diversity of melleolide‐type meroterpenoids produced by Armillaria ostoyae, one of the largest and oldest organisms on Earth, using extracts from liquid and solid fermentation media. The study unveiled three unprecedented dimeric bismelleolides (1‐3) and three novel fatty acid‐substituted congeners (4‐6), along with 11 new (7‐17) and 21 known (18‐38) derivatives. Structure elucidation was done by 1D‐ and 2D‐NMR spectroscopy, HRESI‐MS data, and ROESY spectral analysis for relative configurations. Absolute configurations were determined through crystal structures and ECD spectra comparison. A compound library of melleolide‐type meroterpenoids facilitated metabolomics‐wide associations, revealing production patterns under different culture conditions. The library enabled assessments of antimicrobial and cytotoxic activities, unveiling that the Δ2,4 double bond is not crucial for antifungal activity. Cytotoxicity was linked to the presence of an aldehyde at C‐1, but lost with a hydroxylation at C‐13. Chemoinformatic analyses demonstrated the intricate interplay of chemical modifications on biological properties. This study marks the first systematic exploration of Armillaria spp. meroterpenoid diversity via MS‐based untargeted metabolomics, offering insights into structure‐activity relationships through innovative chemoinformatics.

Omnipolyphilins A and B: Chlorinated Cyclotetrapeptides and Naphtho-α-pyranones from the Plant Nematode-Derived Fungus Polyphilus sieberi

“…For this purpose, it might even be feasible to use modern metabolomics techniques as recently employed for a strain of the basidiomycete Armillaria. Polyphilus spp., however, should perhaps not be further pursued with priority for biocontrol purposes because several of the metabolites we have encountered may be potentially harmful for beneficial organisms, and even the production of the marketed antibiotic drugs of the fusidic acid type, which were finally identified as major antibacterial principles, may pose a risk that can lead to antimicrobial resistance against the antibiotic among soil bacteria.…”

Comparison of the Secondary Metabolism of the Basidiomycetes Armillaria mellea and Desarmillaria ectypa

“…[6] Our recent case study on A. ostoyae has revealed that a single strain can produce over 40 different derivatives of this type. [7] Desarmillaria, a genus containing species that are morphologically similar to those of Armillaria, was segregated from the latter genus by Herink (1973) based on comparative morphol-ogy. It has recently been confirmed that this segregation was valid based on polyphasic taxonomy including multi-locus phylogenetic studies.…”