Biosynthetic crosstalk: Most gene clusters in fungi are orphans with no known associated metabolites. NMR-based comparative metabolomics was used to identify the products of two highly homologous orphan clusters in Aspergillus flavus. The two clusters encode partially redundant biosynthetic pathways that produce overlapping sets of novel fungal alkaloids, feature NRPS-like genes with unusual functions, and regulate fungal development. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.