Cytochrome P450 and O-methyltransferase catalyze the final steps in the biosynthesis of the anti-addictive alkaloid ibogaine from Tabernanthe iboga
Journal of Biological Chemistry July 20, 2018 Scott C. Farrow, Mohamed O. Kamileen, Jessica Meades et al. 55 citations
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.