Convergent biosynthesis of psilocybin in an ectomycorrhizal lineage: is the psychoactive end-product the selected trait?

Mellica Zahra Askari , Varun Surapaneni

The fungivore-deterrence hypothesis, that psilocybin evolved as a chemical defence against arthropod fungivores via 5-HT receptor agonism, has become the working consensus in fungal chemical ecology, despite resting on a phylogenomic pattern of horizontal gene transfer among saprotrophs and remarkably little direct experimental evidence. Recent biochemistry shows that the ectomycorrhizal Inocybe corydalina assembles psilocybin through a convergently evolved, non-homologous ips cluster whose branched pathway yields baeocystin, not psilocybin, as the primary end-product. We argue that psilocybin's psychoactivity at vertebrate 5-HT2A receptors is plausibly incidental, with selection most likely acting on the injury-triggered polymerized indoloquinoid end-state of the blueing reaction (with psilocybin functioning as its stable storage precursor) and only secondarily on the monomeric congeners baeocystin or aeruginascin. We propose a five-tier comparative experimental program to adjudicate among these alternatives.