Enzymatic Synthesis of Psilocybin
Janis Fricke, Felix Blei, Dirk Hoffmeister
Angewandte Chemie International Edition August 1, 2017 DOI: 10.1002/anie.201705489 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Tryptamine Enzyme Biosynthesis Biochemistry Tryptophan Stereochemistry |
| Citations | 210 |
| Key points | Four enzymes—PsiD, PsiK, PsiM, and PsiH—catalyze the biosynthesis of psilocybin from L-tryptophan, and a combined PsiD/PsiK/PsiM reaction produces psilocybin from 4-hydroxy-L-tryptophan. |
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.