Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity

Significance Metal homeostasis is an integral part of metabolism for any organism. A vast array of natural products are already known to mediate iron homeostasis in fungi and bacteria; however, unlike their bacterial counterparts, to date, there are no known fungal small molecules that function to maintain copper homeostasis. Discovery of copper-binding xanthocillins produced by Aspergillus fumigatus gives insight into mechanisms other than the extensively studied copper transporters or metalloproteins for how fungi can regulate copper. This has important ecological implications, as securing scarce nutrients is central for fitness and survival. Conservation of the xanthocillin biosynthetic machinery across filamentous fungal taxa offers a new paradigm in eukaryotic metal homeostasis.