Angewandte Chemie (International ed. in English)
July 20, 2020
Sebastian Obermaier, Michael Müller
59 citations
The fly agaric mushroom, Amanita muscaria, produces the psychoactive compounds ibotenic acid and muscimol, but their biosynthetic pathway and the enzymes involved were unknown. Fifty years ago, researchers hypothesized that the pathway begins with 3-hydroxyglutamate. This work identifies and recombinantly produces a glutamate hydroxylase from A. muscaria, supporting that hypothesis. The hydroxylase gene is flanked by six additional biosynthetic genes, which genomic and transcriptomic data link to ibotenic acid and muscimol production. These results pinpoint the genetic basis for ibotenic acid formation, resolving a decades-old question about a centuries-old drug.
Angewandte Chemie (International ed. in English)
June 27, 2022
Hubert Gerwe, Feng He, Eline Pottie et al.
21 citations
Classical psychedelics alter consciousness by activating the 5-HT2A receptor in the brain, but the precise mechanism is not fully understood. To study this receptor's signaling with high spatiotemporal precision, researchers designed photoswitchable ligands based on the psychedelic N,N-dimethyltryptamine (DMT). By incorporating the DMT-indole ring into a photoswitchable system, they created red-shifted ligands operable by visible light. Among these azo-DMTs, compound 2h (Photo-DMT) stands out: its cis isomer shows DMT-like activity, while the trans isomer acts as a weak partial agonist. This cis-on efficacy switch expands the pharmacological toolbox for investigating the complex signaling of the 5-HT2A receptor.
Angewandte Chemie (International ed. in English)
June 10, 2025
Mohamed O Kamileen, Benke Hong, Klaus Gase et al.
11 citations
Three cytochrome P450 enzymes in the medicinal plant Catharanthus roseus transform the central intermediate 19E-geissoschizine into four distinct alkaloid scaffolds: strychnos, sarpagan, akuammiline-type, and mavacurane-type alkaloids. In vitro enzymatic assays and gene silencing demonstrate this oxidative rearrangement. Mutational analysis shows that minimal changes to the active sites of these similar enzymes modulate product specificity. Substrate reactivity and enzyme mutations work synergistically to generate chemical diversity in monoterpene indole alkaloid biosynthesis.