Psilocybin, the prodrug of the psychedelic compound psilocin, is produced by a phylogenetically scattered group of mushroom-forming fungi in the Agaricales. A psilocybin gene cluster was discovered in three hallucinogenic mushroom genomes, and evidence indicates its horizontal transfer between fungal lineages. The distribution and transmission patterns suggest that psilocybin synthesis may have provided a fitness advantage in dung and late wood-decay niches, which may serve as reservoirs of fungal indole-based metabolites that alter the behavior of mycophagous and wood-eating invertebrates. These genomes will serve as models in neurochemical ecology, advancing the prospecting and synthetic biology of novel neuropharmaceuticals.
Some entomopathogenic fungi keep their insect hosts alive while releasing spores, a behavior that improves spore dispersal. Metabolomics of four populations of periodical cicadas infected with Massospora cicadina revealed the plant-associated amphetamine cathinone, while annual cicadas infected with Massospora platypediae or Massospora levispora contained the mushroom-associated tryptamine psilocybin; the latter two fungi appear to be a single species. The absence of certain fungal enzymes needed to produce cathinone and psilocybin, along with undetectable intermediate metabolites or gene orthologs, suggests novel biosynthesis pathways in Massospora. The neurogenic activity of these compounds indicates that the extended phenotype of Massospora, which alters cicada behavior to maximize spore dissemination, is chemically induced.