Wheldone: A Tale of Two Fungal Cultures

Abstract: Fungi grow in competitive environments, and to cope, they have evolved strategies, such as the ability to produce a wide range of secondary metabolites. How secondary metabolites influence fungal ecology and interspecific interactions, and can these interspecific interactions provide a way to “see” how fungi respond, chemically, within a competitive environment are questions that are poorly addressed. To explore this idea and gain insights into the secondary metabolites produced by fungi, we co-cultured Aspergillus fischeri, a genetically tractable fungus known for producing a range of mycotoxins, with Xylaria flabelliformis, a fungus that produces the fungistatic compound and FDA-approved drug griseofulvin. To monitor and characterize the chemical interactions within the co-culture, we utilized a droplet-liquid microjunction-surface sampling probe (droplet probe), a mass spectrometry mapping technique. The droplet probe extracts samples from defined locations on the co-culture surface, allowing us to analyze the secondary metabolite profile using liquid chromatography-mass spectrometry. As a result of further investigation of this study, we isolated a new compound called wheldone, which is a novel scaffold exhibiting cytotoxic activity against breast, ovarian, and melanoma cancer cell lines. However, the low yields and challenges associated with the co-culture process hindered the large-scale production of wheldone. This scarcity of material also further limits isolation of analogues and pharmacological investigations. In my talk, I will discuss the results of mapping interspecific fungal interactions; the discovery of wheldone; and the progress we have made in scaling up its production.