Biosynthesis of strychnine

Strychnine is a natural product that, through isolation, structural elucidation and synthetic efforts, shaped the field of organic chemistry. Currently, strychnine is used as a pesticide to control rodents because of its potent neurotoxicity. The polycyclic architecture of strychnine has inspired chemists to develop new synthetic transformations and strategies to access this molecular scaffold, yet it is still unknown how plants create this complex structure. Here we report the biosynthetic pathway of strychnine, along with the related molecules brucine and diaboline. Moreover, we successfully recapitulate strychnine, brucine and diaboline biosynthesis in Nicotiana benthamiana from an upstream intermediate, thus demonstrating that this complex, pharmacologically active class of compounds can now be harnessed through metabolic engineering approaches.

Benke Hong, Dagny Grzech, Lorenzo Caputi, Prashant Sonawane, Carlos E. Rodríguez López, Mohamed Omar Kamileen, Néstor J. Hernández Lozada, Veit Grabe, Sarah E. O’Connor