Hypothesized origins of major fungal NRPS subfamilies based on the oldest member of each subfamily. Subfamilies color coded as in Fig. 1. AAR, and ChNPS11/ETPmodule 1 and ChNPS12/ETP module 2 likely originated prior to or early in the divergence of fungi. AAR genes are present in all fungi, while the ChNPS11/ETP/ChNPS12 clade contains representatives of the most ancestral fungal group, the Chytridiomycota. as well as bacterial sequences that nest with high bootstrap support within this clade. Although ACV genes are clearly present in eubacteria, they appear to have been horizontally transferred to euascomycete fungi, hence their dual placement. The CYCLO, ChNPS10, and SID subfamilies were found in Basidiomycota, Schizosaccharomycota, and Euascomycota and thus likely originated in an ancestor of the Dikarya. Fungal PKS;NRPS hybrids and EAS were found only in Euascomycetes.