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.
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.