Biosynthesis of an Anti-Addiction Agent from the Iboga Plant
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.