A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate

Evangelos C. Tatsis, Inês Carqueijeiro, Thomas Dugé de Bernonville, Jakob Franke, Thu-Thuy T. Dang, Audrey Oudin, Arnaud Lanoue, Florent Lafontaine, Anna K. Stavrinides, Marc Clastre, Vincent Courdavault () and Sarah E. O’Connor ()
Additional contact information
Evangelos C. Tatsis: Norwich Research Park
Inês Carqueijeiro: Université François-Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales
Thomas Dugé de Bernonville: Université François-Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales
Jakob Franke: Norwich Research Park
Thu-Thuy T. Dang: Norwich Research Park
Audrey Oudin: Université François-Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales
Arnaud Lanoue: Université François-Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales
Florent Lafontaine: Université François-Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales
Anna K. Stavrinides: Norwich Research Park
Marc Clastre: Université François-Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales
Vincent Courdavault: Université François-Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales
Sarah E. O’Connor: Norwich Research Park

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Monoterpene indole alkaloids comprise a diverse family of over 2000 plant-produced natural products. This pathway provides an outstanding example of how nature creates chemical diversity from a single precursor, in this case from the intermediate strictosidine. The enzymes that elicit these seemingly disparate products from strictosidine have hitherto been elusive. Here we show that the concerted action of two enzymes commonly involved in natural product metabolism—an alcohol dehydrogenase and a cytochrome P450—produces unexpected rearrangements in strictosidine when assayed simultaneously. The tetrahydro-β-carboline of strictosidine aglycone is converted into akuammicine, a Strychnos alkaloid, an elusive biosynthetic transformation that has been investigated for decades. Importantly, akuammicine arises from deformylation of preakuammicine, which is the central biosynthetic precursor for the anti-cancer agents vinblastine and vincristine, as well as other biologically active compounds. This discovery of how these enzymes can function in combination opens a gateway into a rich family of natural products.

Date: 2017
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DOI: 10.1038/s41467-017-00154-x

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