Proposed biosynthetic pathway to ibogaine in T

Proposed biosynthetic pathway to ibogaine in T. iboga. Tryptophan and geranyl diphosphate undergo multiple transformations (multiple arrows) to yield strictosidine, which undergoes multiple transformations (multiple arrows) to yield the hypothesized reactive intermediate dehydrosecodine. In iboga, dehydrosecodine is thought to undergo cyclization to form the (−)-ibogan scaffold and eventually (−)-coronaridine. Net decarboxylation of coronaridine yields ibogamine, which can then undergo 10- hydroxylation and 10-O-methylation to yield ibogaine. The pathway could also bifurcate through voacangine, whereby net decarboxylation of voacangine could lead to ibogaine. Percentages and arrow thickness indicate the relative activity of I10H and N10OMT for different substrate in the pathway, underscoring the potential routes to ibogaine. Red arrows represent the steps that are the focus of this study.

Publication

Cytochrome P450 and O-methyltransferase catalyze the final steps in the biosynthesis of the anti-addictive alkaloid ibogaine from Tabernanthe iboga. (2018) Scott C. Farrow, et al. J Biol Chem. 2018 Sep 7;293(36):13821-13833. Figure: F2.

Disease mentions