Enzymatic synthesis of psilocybin

This biosynthesis assay (2017) investigated the enzymatic synthesis pathways which produce psilocybin within Psilocybe cubensis and Psilocybe cyanescens, to set the groundwork for pharmaceutical psilocybin production within reverse-engineered microbial hosts.


Introduction: Psilocybin is the psychotropic tryptamine‐derived natural product of Psilocybe carpophores, the so‐called “magic mushrooms”. Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure.

Methods: We characterized four psilocybin biosynthesis enzymes, namely i) PsiD, which represents a new class of fungal l‐tryptophan decarboxylases, ii) PsiK, which catalyzes the phosphotransfer step, iii) the methyltransferase PsiM, catalyzing iterative N‐methyl transfer as the terminal biosynthetic step, and iv) PsiH, a monooxygenase.

Results: In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step‐economic route from 4‐hydroxy‐l‐tryptophan.

Discussion: Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.”

Authors: Janis Fricke, Felix Blei & Dirk Hoffmeister

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