Azaphilones are an important class of fungal metabolites characterized by an oxygenated pyrano-quinone bicylic core and are known to exhibit a broad range of biological activities. While widespread in nature, their biosynthesis has not been thoroughly elucidated. By studying an activated azaphilone gene cluster in Aspergillus niger ATCC 1015, we discovered novel compounds (azanigerones A-F) belonging to this family, as well as answered key questions in its production, including identification of the FAD-dependent hydroxylase responsible for the formation of the characteristic bicylic core. Using this information, we extended our studies to the prolific azaphilone producer, Chaetomium globosum, from which chaetoviridin and chaetomugilin compounds were previously isolated. By genetic and enzymatic characterization of this cluster, we uncovered a new mode of collaboration between two iterative polyketide synthases. The divergent nature of these azaphilone systems provides a good opportunity for engineering natural products by combining elements from these clusters to further diversify this compound scaffold.

Biosynthesis of azaphilones

245th National Meeting (2013)

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