Skeletocutins A-L: Antibacterial Agents from the Kenyan Wood-Inhabiting Basidiomycete, Skeletocutis sp.

Abstract

Fermentation of the fungal strain Skeletocutis sp. originating from Mount Elgon Natural Reserve in Kenya, followed by bioassay guided fractionation led to the isolation of 12 previously undescribed metabolites named skeletocutins A-L (1–5 and 7–13) together with the known tyromycin A (6). Their structures were assigned by NMR spectroscopy complemented by HR-ESIMS. Compounds 1–6 and 11–13 exhibited selective activities against Gram-positive bacteria, while compound 10 weakly inhibited the formation of biofilm of Staphylococcus aureus. The isolated metabolites were also evaluated for inhibition of L-leucine aminopeptidase, since tyromycin A had previously been reported to possess such activities but only showed weak effects. Furthermore, all compounds were tested for antiviral activity against Hepatitis C virus (HCV), and compound 6 moderately inhibited HCV infectivity with an IC50 of 6.6 μM.

Skeletocutins M-Q, biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

“…tyromycin A (6) , a closely related compound to the metabolites 1-5 has been reported before from the cultures of the same fungus (i.e. the corresponding mycelial culture of the specimen that was the subject of the present study [6]) and originally from…”

“…The fungal specimen was collected by C. Decock and J. C. Matasyoh from Mount Elgon National Reserve [6] Dried specimen and corresponding cultures were deposited at MUCL, Louvain-la-Neuve, Belgium, under the accession number MUCL…”

“…Minimum inhibitory concentration (MIC) were determined in serial dilution assays by using several microorganisms, as described previously [5,6]: Gram-positive bacteria:…”

“…A preliminary characterization of the producer organism suggested that it belongs to a new species because neither DNA sequence data in the public domain nor morphological characters matched the previously reported species as compared to the literature The genus Skeletocutis (family Polyporaceae), consists of approximately 40 species and their species grow as a crust on the surface of collapsing wood [7] and mostly occur in the temperate climate zones. In our preceding study, the fungal specimen MUCL56074 has been assigned to the genus Skeletocutis by comparison of morphological and 5.8S/ITS rDNA sequences as reported previously [6]. Strain MUCL56074 represents a hitherto undescribed species, which will be formally described in a separate paper in a mycological journal, pending the examination of type material of other, related species.…”

“…The present study deals with the comparison of the secondary metabolites located in the basidiomes (fruiting bodies) of another putatively new species belonging to the genus Skeletocutis, strain MUCL56074. We have recently reported the known metabolite tyromycin A (6) together with 12 unprecedented congeners, for which we proposed the trivial names, skeletocutins A-L, from a liquid culture of the same fungus [6]. A preliminary characterization of the producer organism suggested that it belongs to a new species because neither DNA sequence data in the public domain nor morphological characters matched the previously reported species as compared to the literature The genus Skeletocutis (family Polyporaceae), consists of approximately 40 species and their species grow as a crust on the surface of collapsing wood [7] and mostly occur in the temperate climate zones.…”