Coupling the use of artificial chromosomes with metabolomics enables the high-throughput linkage of fungal natural products with their biosynthetic gene clusters. This method was used here to identify a novel polyketide–nonribosomal peptide scaffold. The genomes of filamentous fungi contain up to 90 biosynthetic gene clusters (BGCs) encoding diverse secondary metabolites—an enormous reservoir of untapped chemical potential. However, the recalcitrant genetics, cryptic expression, and unculturability of these fungi prevent scientists from systematically exploiting these gene clusters and harvesting their products. As heterologous expression of fungal BGCs is largely limited to the expression of single or partial clusters, we established a scalable process for the expression of large numbers of full-length gene clusters, called FAC-MS. Using fungal artificial chromosomes (FACs) and metabolomic scoring (MS), we screened 56 secondary metabolite BGCs from diverse fungal species for expression in Aspergillus nidulans. We discovered 15 new metabolites and assigned them with confidence to their BGCs. Using the FAC-MS platform, we extensively characterized a new macrolactone, valactamide A, and its hybrid nonribosomal peptide synthetase–polyketide synthase (NRPS–PKS). The ability to regularize access to fungal secondary metabolites at an unprecedented scale stands to revitalize drug discovery platforms with renewable sources of natural products.

Chemical investigation of the extracts of the fruits from Campomanesia xanthocarpa resulted in the isolation of six known compounds identified by NMR and comparison with literature data (2′,4′-dihydroxy-5′-methyl-6′-methoxychalcone (1), 2′,4′-dihydroxy-3′,5′-dimethyl-6′-methoxychalcone (2), 2′-hydroxy-3′-methyl-4′,6′-dimethoxychalcone (3), 2′,6′-dihydroxy-3′-methyl-4′-methoxychalcone (4), 5-hydroxy-7-methoxy-8-methylflavanone (5) and 7-hydroxy-5-methoxy-6-methylflavanone (6)). The considerable antioxidant capacity of the extracts was demonstrated by ORAC-FL and DPPH tests. The antiproliferative assay of the extracts and 5 was done in vitro, against many different cancer cell lines besides a healthy one. The extracts presented low cytotoxicity and the substance demonstrated promising results against all the cancer cell lines tested, with IC₅₀ values ranging from 4.75 to 45.81 µmol L⁻¹. The in vitro trypanocidal activity was evaluated against the epimastigote form of the Y strain of Trypanosoma cruzi and an improvement in the activity of the substances 2 (221.81 µmol L⁻¹) and 5 (61.87 µmol L⁻¹) was observed regarding the values obtained for the extracts. Graphical Abstract