biostudies-literatureUnknown4(8)Semper CGenomics analysis confirmed the status of filamentous fungi as a rich source of novel secondary metabolites; however, the discovery of these compounds is hampered by the cryptic nature of their biosynthetic pathways under laboratory conditions. Consequently, despite substantial research effort over the past decades, much of the secondary metabolome remains uncharacterized in fungal organisms. Our manual curation of biosynthetic gene clusters (BGCs) in the Aspergillus niger NRRL3 genome revealed that only 13 of 86 BGCs have had their cognate secondary metabolite products confirmed or reliably inferred. We also identified 60 transcription factors (TFs) associated with cryptic BGCs. To further characterize A. niger secondary metabolism, we created a collection of strains each overexpressing aPNAS nexuspgaf249https://www.ebi.ac.uk/biostudies/studies/S-EPMC12368960biostudies-literatureGlobal survey of secondary metabolism in <i>Aspergillus niger</i> via activation of specific transcription factors.PMC12368960Ram SSavchenko ABenoit-Gelber IBailey ZPham TTMPalys STsang AMoisan MCSemper COuedraogo JPEvdokias GReid IDi Falco MGeoffrion NfalseGlobal survey of secondary metabolism in <i>Aspergillus niger</i> via activation of specific transcription factors.Genomics analysis confirmed the status of filamentous fungi as a rich source of novel secondary metabolites; however, the discovery of these compounds is hampered by the cryptic nature of their biosynthetic pathways under laboratory conditions. Consequently, despite substantial research effort over the past decades, much of the secondary metabolome remains uncharacterized in fungal organisms. Our manual curation of biosynthetic gene clusters (BGCs) in the Aspergillus niger NRRL3 genome revealed that only 13 of 86 BGCs have had their cognate secondary metabolite products confirmed or reliably inferred. We also identified 60 transcription factors (TFs) associated with cryptic BGCs. To further characterize A. niger secondary metabolism, we created a collection of strains each overexpressing a2025-01-01T00:00:00Z2025 Aug2026-04-08T08:19:05.634Z2026-04-08T00:16:41.326ZS-EPMC123689604085242410.1093/pnasnexus/pgaf249