Fungi synthesize flavonoids, but not isoflavones - a risk of feeding source contamination

Flavonoids, while best known as plant polyphenols, also include several simple structures demonstrably synthesized by fungi. However, claims that fungi produce more structurally advanced flavonoids, particularly isoflavones, remain uncertain. Here we show that commonly used culture‑media components, especially mycological peptone, contain substantial amounts of plant‑derived isoflavones, providing a straightforward explanation for many reported fungal detections. A comparative analysis of available fungal genomic data revealed that early phenylpropanoid pathway homologs (PAL, C4H, 4CL) are widespread, but canonical plant chalcone synthases (CHS) are rare, and their homology is uncertain. Crucially, no fungal genomes encode key downstream plant-type enzymes required for flavanone or isoflavone biosynthesis (CHI, IFS, HID). Instead, genuine fungal flavone production depends on independently evolved NRPS–PKS hybrid synthases confined to specific lineages within the Pezizomycotina (Ascomycota). Thus, fungi can produce flavonoids, but the reports of advanced flavonoids, including isoflavones, in Basidiomycota therefore likely represent artifacts caused by plant-derived substrate contamination.