Biosynthesis of strychnine

Benke Hong, Dagny Grzech, Lorenzo Caputi, Prashant Sonawane, Carlos E. Rodríguez López, Mohamed Omar Kamileen, Néstor J. Hernández Lozada, Veit Grabe and Sarah E. O’Connor ()
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Benke Hong: Max-Planck Institute for Chemical Ecology
Dagny Grzech: Max-Planck Institute for Chemical Ecology
Lorenzo Caputi: Max-Planck Institute for Chemical Ecology
Prashant Sonawane: Max-Planck Institute for Chemical Ecology
Carlos E. Rodríguez López: Max-Planck Institute for Chemical Ecology
Mohamed Omar Kamileen: Max-Planck Institute for Chemical Ecology
Néstor J. Hernández Lozada: Max-Planck Institute for Chemical Ecology
Veit Grabe: Max-Planck Institute for Chemical Ecology
Sarah E. O’Connor: Max-Planck Institute for Chemical Ecology

Nature, 2022, vol. 607, issue 7919, 617-622

Abstract: Abstract 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 rodents1 because of its potent neurotoxicity2,3. The polycyclic architecture of strychnine has inspired chemists to develop new synthetic transformations and strategies to access this molecular scaffold4, 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.

Date: 2022
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DOI: 10.1038/s41586-022-04950-4

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