Isocyanides identified from fungi and architecture of isocyanide synthase-containing gene clusters in A. fumigatus. (A) Examples of isocyanides identified from fungi, including xanthocillin (compound 1), darlucin B (compound 2), isonitrin A (compound 3), isonitrinic acid E (compound 4), A32390A (compound 5), and brassicicolin A (compound 6). (B) The crm gene cluster contains a novel multidomain ICS-NRPS hybrid enzyme. The 4G gene cluster contains two ICS domain genes, icsA and icsB. The xan gene cluster contains an ICS domain gene, xanB. Isocyanide synthases are depicted in blue. Fungal C6 transcription factors are depicted in yellow. Transporters are depicted in black. ThiJ/Pfp1 domain proteins with homology to isocyanide hydratases are depicted in red. P450 monooxygenases are depicted in green. (C) Predicted function of open reading frames (ORFs) within A. fumigatus isocyanide gene clusters.