Enzymatic Synthesis of Psilocybin
Angewandte Chemie International Edition – August 01, 2017
Source: OpenAlex
Summary
For decades, the enzymatic chemistry behind psilocybin, the psychedelic compound in "magic mushrooms," remained a mystery. Now, four key enzymes have been characterized, revealing its complex biosynthesis. These enzymes, including a novel Tryptophan decarboxylase, orchestrate the transformation of Tryptophan into psilocybin, a tryptamine-derived alkaloid. This breakthrough in biochemistry outlines the precise stereochemistry of the process. Understanding this enzymatic pathway is crucial for future chemical synthesis and biotechnological production, especially given renewed interest in psilocybin for drug studies.
Abstract
Abstract 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. 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. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step‐economic route from 4‐hydroxy‐ l ‐tryptophan. Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.