S‐Adenosyl‐l‐Methionine Salvage Impacts Psilocybin Formation in “Magic” Mushrooms
ChemBioChem – December 04, 2019
Source: OpenAlex
Summary
Producing the psychedelic natural product psilocybin is biochemically intensive, requiring one ATP and two SAM equivalents per molecule. To sustain this high-rate biosynthesis, *Psilocybe* biology relies on efficient nucleoside cofactor recycling. Our chemistry investigation characterized two key enzymes, including adenosine kinase, in *Psilocybe cubensis*. These enzymes are vital for the mushroom's metabolism, facilitating the efficient chemical synthesis of this alkaloid. Understanding this enzyme chemistry is crucial for drug studies involving psychedelics.
Abstract
Abstract Psychotropic Psilocybe mushrooms biosynthesize their principal natural product psilocybin in five steps, among them a phosphotransfer and two methyltransfer reactions, which consume one equivalent of 5′‐adenosine triphosphate (ATP) and two equivalents of S ‐adenosyl‐ l ‐methionine (SAM). This short but co‐substrate‐intensive pathway requires nucleoside cofactor salvage to maintain high psilocybin production rates. We characterized the adenosine kinase (AdoK) and S ‐adenosyl‐ l ‐homocysteine (SAH) hydrolase (SahH) of Psilocybe cubensis . Both enzymes are directly or indirectly involved in regenerating SAM. qRT‐PCR expression analysis revealed an induced expression of the genes in the fungal primordia and carpophores. A one‐pot in vitro reaction with the N ‐methyltransferase PsiM of the psilocybin pathway demonstrates a concerted action with SahH to facilitate biosynthesis by removal of accumulating SAH.