Convergent evolution of psilocybin biosynthesis by psychedelic mushrooms

Abstract

Psilocybin is a psychoactive compound with clinical applications produced by dozens of mushroom species1. There has been a longstanding interest in psilocybin research with regard to treatment for addiction2, depression3, and end-of-life suffering4. However, until recently very little was known about psilocybin biosynthesis and its ecological role. Here we confirm and refine recent findings5 about the genes underpinning psilocybin biosynthesis, discover that there is more than one psilocybin biosynthesis cluster in mushrooms, and we provide the first data directly addressing psilocybin’s ecological role. By analysing independent genome assemblies for the hallucinogenic mushrooms Psilocybe cyanescens and Pluteus salicinus we recapture the recently discovered psilocybin biosynthesis cluster5,6 and show that a transcription factor previously implicated in its regulation is actually not part of the cluster. Further, we show that the mushroom Inocybe corydalina produces psilocybin but does not contain the established biosynthetic cluster, and we present an alternative cluster. Finally, a meta-transcriptome analysis of wild-collected mushrooms provides evidence for intra-mushroom insect gene expression of flies whose larvae grow inside Psilocybe cyanescens. These larvae were successfully reared into adults. Our results show that psilocybin does not confer complete protection against insect mycophagy, and the hypothesis that it is produced as an adaptive defense compound may need to be reconsidered.

Monoamine Biosynthesis via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom

“…Pc ncAAAD catalyzes decarboxylation of multiple l -aromatic amino acids into their corresponding monoamine products in vitro ; however, the role and abundance of these specialized metabolites in P. cubensis remain unclear. As psilocybin mushrooms reportedly contain multiple psilocybin-like biosynthetic gene clusters, Pc ncAAAD may operate within one of these gene clusters in the production of psilocybin-like specialized metabolites. Due to difficulties of genetic studies in P. cubensis, we compared the in vivo product formation of Pc ncAAAD against that of previously described AAADs operating in known biosynthetic pathways in the context of transgenic yeast.…”

Psychoactive plant- and mushroom-associated alkaloids from two behavior modifying cicada pathogens

“…Psilocybin may also confer protection against predation, competition, and/or parasitism for a select few insects that exhibit indifference to psilocybin. For example, the dark-winged fungus gnat (Sciaridae), can successfully complete its lifecycle in fruit bodies of psilocybin-containing Psilocybe cyanescens ( Awan et al 2018 ). Likewise, leafcutter ants ( Acromyrmex lobicornis ) have been observed actively foraging on Psilocybe coprophila fruit bodies in Argentina, transporting basidiocarps back into the nest, possibly for defense purposes ( Masiulionis et al, 2013 ).…”

Taking Different Roads: l‐Tryptophan as the Origin of Psilocybe Natural Products

“…(dark winged fungus gnat) completed the entire developmental cycle (i. e., egg to adult) feeding solely on P. cyanescens. [33] Furthermore, psilocybin seems to attenuate the web building behavior of the spider Araneus diadematus. [34] Structurally, psilocin is closely related to 5-HT.…”