Secondary metabolites from the saprotrophic fungus Granulobasidium vellereum
Abstract: The production of secondary metabolites by the saprotrophic fungus Granulobasidium vellereum was investigated. G. vellereum is a wood decomposing basidiomycete fungus that arrives at dead trunks of fallen hard wood trees at a later stage of the decomposition process and hence need to outcompete the organisms already colonizing the site. It was hypothesised that part of the fungus competitive ability was based on the production of secondary metabolites. In total, 33 secondary metabolites, all of sesquiterpenoid origin and comprising structures with the protoilludane, illudane, illudalane or cerapicane carbon skeletal types, were isolated by chromatographic methods and characterized by spectroscopic techniques. Twenty-two of these compounds had previously not been described and of the 11 known compounds two were not previously described as natural products. Four of the new compounds showed potent cytotoxic effects against the Huh7 and MT4 tumour cell lines. The mechanism of action was most likely similar to that of the known alkylating agent illudin M and based on chemical reactivity rather than enzymatic affinity. None of these cytotoxic compounds had any potent anti-fungal effects, perhaps due to them not being able to penetrate the cell walls of the fungi. The compound that had the most anti-fungal effects was the known compound radulone A and thus possibly a part of the molecular defence system of G. vellereum. One of the compounds was found to increase the elongation of lettuce seedlings. G. vellereum was co-cultivated with seven other wood-decay fungi with the aim of investigating the secondary metabolite response of G. vellereum towards other fungi, with regard to up-regulation and de novo production of secondary metabolites. Samples from the co-cultures were taken after 7 to 12 days of incubation and subsequently analysed by LC-HRMS followed by PCA of the data. Nineteen metabolites from G. vellereum were up-regulated in all seven interactions, of these were six identified as previously known metabolites from G. vellereum, one of which was the highly cytotoxic 3S,7S-illudin M. The response of G. vellereum towards the different fungi varied, indicating that G. vellereum has the ability to adapt its response slightly depending on the interacting species.
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