Oxidative Rearrangements of the Alkaloid Intermediate Geissoschizine.
Mohamed O. Kamileen, Benke Hong, Klaus Gase, Maritta Kunert, Lorenzo Caputi, Benjamin R Lichman, Sarah E O'Connor
Angewandte Chemie (International ed. in English) June 10, 2025 DOI: 10.1002/anie.202501323 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Catharanthus roseus enzymes |
| Keywords | Biosynthesis Geissoschizine Natural products Plant p450s Plant enzymes Medicinal plants Pharmaceutical compounds |
| Citations | 11 |
| Key findings | Three cytochrome P450 enzymes in Catharanthus roseus transform 19E-geissoschizine into four distinct alkaloid scaffolds, with minimal active-site mutations modulating product specificity. |
Abstract
Plants can generate structural diversity by enzymatic rearrangement of a central intermediate. 19E-geissoschizine is one such chemically versatile intermediate that plays a central role in the biosynthesis of monoterpene indole alkaloids such as strychnine, ibogaine, and vinblastine. Here we report how 19E-geissoschizine undergoes oxidative transformations to generate four distinct alkaloid scaffolds through the action of three biosynthetic enzymes. Using in vitro enzymatic assays and gene silencing, we demonstrate how these three cytochrome P450 enzymes in the medicinal plant Catharanthus roseus transform 19E-geissoschizine into strychnos, sarpagan, akuammiline-type, and mavacurane-type alkaloids. We use mutational analysis to show how minimal changes to the active site of these similar enzymes modulate product specificity. This work highlights how substrate reactivity and enzyme mutations work synergistically to generate chemical diversity.