Exploring the Secondary Metabolism of Basidiomycota: Unveiling Novel Bioactive and Chemically Diverse Compounds

Basidiomycota, the second largest division of the fungal kingdom, exhibit remarkable chemical and biological diversity. They play crucial ecological roles as decomposers, mycorrhizal symbionts, and plant pathogens, highlighting their significance in ecosystems. Additionally, Basidiomycota are well-known to produce a wide array of secondary metabolites, including polyketides, terpenoids, alkaloids, and peptides, contributing to their diverse ecological roles.
These compounds possess various biological activities such as antimicrobial, antitumor and antiviral, making Basidiomycota a valuable resource for drug discovery and biotechnological applications.
This thesis comprises the investigations on the secondary metabolism of four different Basidiomycota, including Armillaria ostoyae, Guyanagaster necrorhiza, Heimiomyces sp. and Perenniporia centrali-africana. For this purpose, these fungi were cultivated under different growth conditions, mainly liquid and solid fermentation. Extracts that were obtained from these cultivations were separated by preparative high performance liquid chromatography (HPLC) after evaluation of the corresponding analytical HPLC-DAD/MS profiles. The planar structures of the purified compounds were elucidated by 1D and 2D NMR spectroscopy in addition to HR-ESI-MS data. Relative configurations were assigned by analysis of ROESY spectra, while absolute configurations were derived by the synthesis of MTPA esters or from
crystal structures and ECD spectra comparison of related known derivatives. This led to the identification of a total of 34 new secondary metabolites and 37 known derivatives from the organisms under investigation. A. ostoyae was given a special role in this, because its secondary metabolism was systematically explored by MS-based untargeted metabolomics, providing insights into the diversity of the compound class of the sesquiterpene aryl esters.
All isolated compounds were analyzed for their i) antibacterial activities in a serial dilution assay against fungal strains, Gram-positive and Gram-negative bacteria and ii) for their cytotoxicity against different cancer cell lines. These data were utilized not only for assessing bioactivities but also for identifying potential structure-activity relationships (SARs) through comparative analysis, which was especially supported by cheminformatic methods in the case of A. ostoyae. In summary, all findings demonstrated the importance of Basidiomycota as a prolific resource for the discovery and production of new bioactive natural products.