Directed Biosynthesis of Mitragynine Stereoisomers

Schotte, C.; Jiang, Y.; Grzech, D.; Dang, T.; Laforest, L.; Leon, F.; Mottinelli, M.; Nadakuduti, S. S.; McCurdy, C. R.; O'Connor, S. E.

doi:10.1101/2022.12.22.521574

bioRxiv · 10.1101/2022.12.22.521574

Directed Biosynthesis of Mitragynine Stereoisomers

Schotte, C.·Jiang, Y.·Grzech, D.·Dang, T.·Laforest, L.·Leon, F.·Mottinelli, M.·Nadakuduti, S. S.·McCurdy, C. R.·O'Connor, S. E.

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Abstract

Mitragyna speciosa ("Kratom") is used as a natural remedy for pain and management of opioid dependence. The pharmacological properties of Kratom have been linked to a complex mixture of monoterpene indole alkaloids, most notably mitragynine. Here, we report the central biosynthetic steps responsible for the scaffold formation of mitragynine and related corynanthe-type alkaloids. We illuminate the mechanistic basis by which the key stereogenic centre of this scaffold is formed. These discoveries were leveraged for the enzymatic production of mitragynine, the C-20 epimer speciogynine, and a series of fluorinated analogues.

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Schotte, C., Jiang, Y., Grzech, D., Dang, T., Laforest, L., Leon, F., Mottinelli, M., Nadakuduti, S. S., McCurdy, C. R., O'Connor, S. E.. 2022-12-22. Directed Biosynthesis of Mitragynine Stereoisomers. https://doi.org/10.1101/2022.12.22.521574

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