Reappraising the structures and distribution of metabolites from black aspergilli containing uncommon 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one systems.

To date, natural products containing 2-benzyl-4H-pyran-4-one and 2-benzylpyridin-4(1H)-one substructures have been encountered in relatively few fungi outside of the black aspergilli clade. While exploring the occurrence of these compounds among Aspergillus spp., it was determined that the structures of the unusual furopyrrols tensidols A and B (5 and 6) and JBIR-86 and JBIR-87 (9 and 10) were incorrect and should be reassigned as 2-benzyl-4H-pyran-4-ones (7, 8, 11e, and 12, respectively). The origin of the unique N-phenyl groups in the 2-benzylpyridin-4(1H)-ones nygerones A and B (1 and 2) were also examined, and it was established that N-phenylamides added to the culture medium were suitable substrates for generating these metabolites; however, this phenomenon remained limited to a single fungus in our collection (Aspergillus niger ATCC 1015). A variety of 2-benzyl-4H-pyran-4-ones and 2-benzylpyridin-4(1H)-ones were detected among the black aspergilli, but only pestalamide B (13) was found in all 11 of the tested strains. These metabolites, as well as a group of synthetic analogues, demonstrated weak antifungal activity against several Candida strains, Aspergillus flavus, and Aspergillus fumigatus.

Reassessing the ichthyotoxin profile of cultured Prymnesium parvum (golden algae) and comparing it to samples collected from recent freshwater bloom and fish kill events in North America.

Within the last two decades, Prymnesium parvum (golden algae) has rapidly spread into inland waterways across the southern portion of North America and this organism has now appeared in more northerly distributed watersheds. In its wake, golden algae blooms have left an alarming trail of ecological devastation, namely massive fish kills, which are threatening the economic and recreational value of freshwater systems throughout the United States. To further understand the nature of this emerging crisis, our group investigated the chemical nature of the toxin(s) produced by P. parvum. We approached the problem using a two-pronged strategy that included analyzing both laboratory-grown golden algae and field-collected samples of P. parvum. Our results demonstrate that there is a striking difference in the toxin profiles for these two systems. An assemblage of potently ichthyotoxic fatty acids consisting primarily of stearidonic acid was identified in P. parvum cultures. While the concentration of the fatty acids alone was sufficient to account for the rapid-onset ichthyotoxic properties of cultured P. parvum, we also detected a second type of highly labile ichthyotoxic substance(s) in laboratory-grown golden algae that remains uncharacterized. In contrast, the amounts of stearidonic acid and its related congeners present in samples from recent bloom and fish kill sites fell well below the limits necessary to induce acute toxicity in fish. However, a highly labile ichthyotoxic substance, which is similar to the one found in laboratory-grown P. parvum cultures, was also detected. We propose that the uncharacterized labile metabolite produced by P. parvum is responsible for golden algae's devastating fish killing effects. Moreover, we have determined that the biologically-relevant ichthyotoxins produced by P. parvum are not the prymnesins as is widely believed. Our results suggest that further intensive efforts will be required to chemically define P. parvum's ichthyotoxins under natural bloom conditions.

A chemical epigenetics approach for engineering the in situ biosynthesis of a cryptic natural product from Aspergillus niger.

A new fungal metabolite, nygerone A (), featuring a unique 1-phenylpyridin-4(1H)-one core that had previously not been reported from any natural source, has been obtained from Aspergillus niger using a chemical epigenetics methodology.

Epigenetic remodeling of the fungal secondary metabolome.

Fungi treated with DNA methyltransferase and histone deacetylase inhibitors exhibited natural product profiles with enhanced chemical diversity demonstrating that small-molecule epigenetic modifiers are effective tools for rationally controlling the native expression of fungal biosynthetic pathways and generating new biomolecules.