Chemistry. 2019 Nov 14. doi: 10.1002/chem.201904363. [Epub ahead of print]
1Department Pharmaceutical Microbiology, Hans Knöll Institute, Friedrich Schiller University, Beutenbergstrasse 11a, 07745, Jena, Germany.2Department Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology-Hans Knöll Institute, Beutenbergstrasse 11a, 07745, Jena, Germany.3Transfer Group Anti-Infectives, Leibniz Institute for Natural Product, Research and Infection Biology-Hans Knöll Institute, Beutenbergstrasse 11a, 07745, Jena, Germany.4Faculty of Biological Sciences, Friedrich Schiller University, Jena, 07745, Jena, Germany.
The psychotropic effects of Psilocybe “magic” mushrooms are caused by the l-tryptophan-derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other l-tryptophan-derived β-carbolines as their natural products, which was confirmed by 1D and 2D NMR spectroscopy. Stable-isotope labeling with 13 C11 -l-tryptophan verified the β-carbolines as biosynthetic products of these fungi. In addition, MALDI-MS imaging showed that β-carbolines accumulate toward the hyphal apices. As potent inhibitors of monoamine oxidases, β-carbolines are neuroactive compounds and interfere with psilocybin degradation. Therefore, our findings represent an unprecedented scenario of natural product pathways that diverge from the same building block and produce dissimilar compounds, yet contribute directly or indirectly to the same pharmacological effects.
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
alkaloids; ayahuasca; beta-carboline; natural products; psilocybinPMID: 31729089 DOI: 10.1002/chem.201904363