Directed Biosynthesis of Mitragynine Stereoisomers

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 center of this scaffold is formed. These discoveries were leveraged for the enzymatic production of mitragynine, the C-20 epimer speciogynine, and fluorinated analogues.

Automated summary

The central biosynthetic steps responsible for the formation of mitragynine and related alkaloids in Mitragyna speciosa (kratom) have been identified, shedding light on the mechanistic basis and enabling the enzymatic production of these compounds.