Journal of Biological Chemistry
July 20, 2018
Scott C. Farrow, Mohamed O. Kamileen, Jessica Meades et al.
55 citations
Two enzymes that complete the biosynthesis of ibogaine, an alkaloid from the iboga plant used traditionally in equatorial Africa and known for alleviating opioid withdrawal, have been identified. Using the first iboga transcriptome generated by next-generation sequencing and homology-guided gene discovery, the researchers found ibogamine 10-hydroxylase (I10H) and noribogaine-10-O-methyltransferase (N10OMT). When expressed in yeast or bacteria and incubated with precursor compounds, both enzymes performed the predicted chemical steps, confirmed by HPLC–MS analysis. Their transcripts were abundant in ibogaine-producing plant tissues. These discoveries and the publicly available transcriptome may help stabilize the ibogaine supply through synthetic biology and support its development as an addiction treatment.
ChemBioChem
August 24, 2023
Eike Schäfer, Stefan Bartram, Felix Trottmann et al.
7 citations
Psilocybe 'magic mushrooms' are well known for their psychotropic tryptamines, but the diversity of other specialized metabolites, especially terpenoids, has remained unclear. CubA, the single clade II sesquiterpene synthase from Psilocybe cubensis, was produced in Escherichia coli and characterized in vitro, with additional in vivo assays in Aspergillus niger. GC-MS analyses showed CubA functions as a multi-product synthase, producing cubebol, β-copaene, δ-cadinene, and germacrene D as major products depending on reaction conditions. Analysis of mature P. cubensis mushrooms detected β-copaene and δ-cadinene. Closely related enzymes are encoded in genomes of various Psilocybe species, providing insight into the metabolic capacity of the entire genus.
ChemBioChem
May 3, 2025
Nick Zschoche, Markus Gressler, Stefan Bartram et al.
1 citation
Psilocybe cubensis mushrooms, famous for producing the psychedelic compound psilocybin, also possess enzymes that synthesize a variety of other small, potentially bioactive molecules. Four newly identified sesquiterpene synthases, CubB through CubE, are expressed differently in the mushroom's fruiting bodies versus its vegetative mycelium. CubB produces a single compound, nerolidol, while CubC generates multiple sesquiterpenes including β-caryophyllene and α-humulene. CubD and CubE nearly exclusively produce sterpurene. The presence of nerolidol was confirmed in young fruiting bodies and vegetative mycelium. These findings expand understanding of the secondary metabolome of Psilocybe species.
ChemBioChem
April 1, 2026
Sebastian Schober, Lisa Dorfmann, Karl Walther et al.
Psilocybe cubensis magic mushrooms produce not only the psychedelic psilocybin but also a range of sesquiterpenes, natural products that can modulate biological receptors. Five sesquiterpene synthases were characterized: CubF makes α-muurolol, CubG1 and CubG2 produce mainly epi-isozizaene and β-duprezianene, CubH yields dauca-4(11),8-diene, and CubI forms β-barbatene. Gas chromatography revealed that vegetative mycelium and fruiting bodies have different sesquiterpene profiles, with sterpurene prominent in mycelium and dauca-4(11),8-diene in fruiting bodies. This knowledge may help separate the pharmacological effects of whole magic mushrooms from those of pure psilocybin.
bioRxiv Preprint Server
May 26, 2019
Scott C. Farrow, Mohamed O. Kamileen, Lorenzo Caputi et al.
preprint
The psychoactive plant compounds (−)-ibogaine and (−)-voacangine show promise for treating opioid addiction but are difficult to obtain from natural sources. Researchers report the complete biosynthesis of (−)-voacangine and its de-esterified form, which can be converted to (−)-ibogaine by heating. This discovery enables production of these compounds through synthetic biology. Notably, these compounds have the opposite enantiomeric configuration compared to other major alkaloids in their class. The identification of the biosynthetic enzymes reveals how nature produces both enantiomeric series of this medically important alkaloid scaffold using closely related enzymes, including those that catalyze enantioselective formal Diels-Alder reactions.