Identification of clerodane diterpene modifying cytochrome P450 (CYP728D26) in Salvia divinorum - en route to psychotropic salvinorin A biosynthesis.
Physiologia plantarum January 1, 2024 Iris Ngo, Rahul Kumar, Liang Li et al. 6 citations
A newly identified enzyme, CYP728D26, catalyzes a specific oxygenation step in the biosynthesis of salvinorin A, a potent κ-opioid receptor agonist from the hallucinogenic plant Salvia divinorum. This enzyme acts on crotonolide G, a compound with a clerodane backbone, and has a Michaelis constant (Km) of 13.9 μM. A close relative, CYP728D25, shows activity only in yeast overexpression systems but not in purified assays, highlighting the need for cautious interpretation of such results. Understanding this pathway could enable biomanufacturing of semi-synthetic derivatives for developing alternative, non-opioid pain relievers targeting the κ-opioid receptor.