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Journal Article

Biosynthesis of an anti-addiction agent from the iboga plant

MPS-Authors
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Kamileen,  Mohamed Omar
Department of Natural Product Biosynthesis, Prof. Dr. Sarah O'Connor, MPI for Chemical Ecology, Max Planck Society;
IMPRS on Ecological Interactions, MPI for Chemical Ecology, Max Planck Society;

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Caputi,  Lorenzo
Department of Natural Product Biosynthesis, Prof. Dr. Sarah O'Connor, MPI for Chemical Ecology, Max Planck Society;

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O’Connor,  Sarah E.
Department of Natural Product Biosynthesis, Prof. Dr. Sarah O'Connor, MPI for Chemical Ecology, Max Planck Society;

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SOC088.pdf
(Publisher version), 2MB

Supplementary Material (public)

SOC088s1.zip
(Supplementary material), 4MB

Citation

Farrow, S. C., Kamileen, M. O., Caputi, L., Bussey, K., Mundy, J. E. A., McAtee, R. C., et al. (2019). Biosynthesis of an anti-addiction agent from the iboga plant. Journal of the American Chemical Society, 141(33), 12979-12983. doi:10.1021/jacs.9b05999.


Cite as: http://hdl.handle.net/21.11116/0000-0003-B296-A
Abstract
(−)-Ibogaine and (−)-voacangine are plant derived psychoactives that show promise as effective treatments for opioid addiction. However, these compounds are produced by hard to source plants making these chemicals difficult for broad-scale use. Here we report the complete biosynthesis of (−)-voacangine, and de-esterified voacangine, which is converted to (−)-ibogaine by heating. This discovery will enable production of these compounds by synthetic biology methods. Notably, (−)-ibogaine and (−)-voacangine are of the opposite enantiomeric configuration compared to the other major alkaloids found in this natural product class. Discovery of these biosynthetic enzymes therefore demonstrates how nature generates both enantiomeric series of this medically important alkaloid scaffold using closely related enzymes, including those that catalyze enantioselective formal Diels-Alder reactions. One Sentence Summary Biosynthesis of iboga alkaloids with anti-addiction promise reveals enantioselectivity of enzymatic Diels-Alder reactions.