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Enzymatic Synthesis of Psilocybin.
Janis Fricke1, Felix Blei1, Dirk Hoffmeister1
1Department Pharmaceutical Microbiology at the Hans Knöll Institute, Friedrich-Schiller-Universität, Beutenbergstrasse 11a, 07745, Jena, Germany.
Angewandte Chemie (International Ed. in English)
|August 2, 2017
Summary
Researchers identified key enzymes for psilocybin biosynthesis in magic mushrooms. This discovery may enable future biotechnological production of psilocybin for pharmaceutical use.
Area of Science:
- Biochemistry
- Mycology
- Natural Product Synthesis
Background:
- Psilocybin, a psychoactive compound from "magic mushrooms", has a known structure but an unknown biosynthetic pathway.
- Despite decades of research, the enzymes responsible for psilocybin production remain unidentified.
Purpose of the Study:
- To elucidate the enzymatic basis of psilocybin biosynthesis.
- To identify and characterize the enzymes involved in the psilocybin pathway.
- To lay the groundwork for potential biotechnological production of psilocybin.
Main Methods:
- Enzyme characterization of four key proteins: PsiD, PsiK, PsiM, and PsiH.
- Reconstitution of the psilocybin biosynthetic pathway using identified enzymes.
- In vitro enzymatic synthesis of psilocybin from 4-hydroxy-l-tryptophan.
Main Results:
- PsiD identified as a novel fungal l-tryptophan decarboxylase.
- PsiK characterized as the phosphotransferase enzyme.
- PsiM identified as a methyltransferase catalyzing iterative N-methylation.
- PsiH identified as a monooxygenase.
- Enzymatic synthesis of psilocybin achieved in a multi-step reaction (PsiD/PsiK/PsiM).
Conclusions:
- The enzymatic pathway for psilocybin biosynthesis has been elucidated.
- Four key enzymes (PsiD, PsiK, PsiM, PsiH) have been identified and characterized.
- The findings provide a foundation for the biotechnological production of psilocybin, relevant to its growing pharmaceutical interest.