Probing selected European and Kenyan Basidiomycota, towards the discovery of novel bioactive natural products
Creators: name: Sum, Winnie Chemutai
Publisher: name: Zenodo
Year: 2024

description: Human beings have relied on natural products as their medicine cabinet since time immemorial. Until now, 70% of the drugs in use were obtained directly or indirectly from natural sources. Nonetheless, human ailments continue to cause significant morbidity and mortality in the present-day despite the major advances made in modern medicine. In particular, cardiovascular diseases, cancer, neurodegenerative diseases and infectious diseases are the top most killer diseases in our world today. Furthermore, the existing drug resistance threat by microbes underscores the need for molecules with new chemistry to supplement the drying-up antibiotic development pipeline. Thus, there is a dire need to dig deeper into unexplored niches for potential new drugs. Fungi of the phylum Basidiomycota have proven to be prolific producers of natural products with health-promoting effects. The fungi are highly biodiverse especially in the tropics but understudied compared to the Ascomycota, and their knowledge is still incomplete even in the hugely explored temperate zones. Thus, a multitude of undescribed species still exists, and a small portion of the fungal phylum has been examined so far for their production of valuable secondary metabolites.The current thesis mainly focused on the characterization of bioactive molecules yielded by selected basidiomycetes of the temperate and tropical regions. The producer strains of the compounds featured in various publications comprising the thesis originated from Germany, Finland and Kenya. Their taxonomic identifications were based on morphological and molecular characteristics, in addition to their chemical profiles. The isolated compounds were screened for their antimicrobial, cytotoxic and neurotrophic effects, leading to the discovery of various bioactive molecules. The structures of the compounds were majorly characterized using NMR spectroscopy and mass spectrometry coupled with database searches in the dictionary of natural products (DNP) and SciFinder. In total, thirty-three previously undescribed compounds in addition to several known ones were obtained.From the Kenyan Abundisporus violaceus and German Dentipellis fragilis, fourteen drimane-type sesquiterpenoids were obtained. Most compounds demonstrated neurotrophic effects in the neurite-outgrowth assays and/or stimulated the increased production of neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in astrocytoma cells. Ten further cyathane-xyloside diterpenoids were also derived from D. fragilis, with various antimicrobial and cytotoxic activities. Additionally, similar bioactivities were demonstrated by the lanostanoid triterpenes and lactone derivatives isolated from the African Fomitopsis carnea and European Bondarzewia mesenterica, respectively. Furthermore, two species of the genus Hericium namely H. coralloides and H. flagellum collected from KÄÄPÄ Biotech (Finland) and Bavaria National Park (Germany), respectively, yielded ten unprecedented isoindolinone and benzofuranone derivatives with strong neurotrophic effects and no cytotoxicity, as well as weak or no antimicrobial activities. In the course of the current research, we also reviewed the Basidiomycota majorly based on the chemistry of its secondary metabolites reported over a period of five years (2019-2023). We identified that over three hundred and fifty bioactive compounds were isolated majorly from Asia and Africa, with few European records. Thus underscoring the fact that the world’s untapped regions remain lucrative harbors of useful basidiomycete metabolites.In summary, the results obtained from our research undoubtedly reiterates the high potential of the Basidiomycota as a great reservoir of novel bioactive agents that could act as leads towards the development of new drug molecules.