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- Title
A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate.
- Authors
Tatsis, Evangelos C.; Carqueijeiro, Inês; de Bernonville, Thomas Dugé; Franke, Jakob; Dang, Thu-Thuy T.; Oudin, Audrey; Lanoue, Arnaud; Lafontaine, Florent; Stavrinides, Anna K.; Clastre, Marc; Courdavault, Vincent; O'Connor, Sarah E.
- 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.
- Subjects
BIOACTIVE compounds; MONOTERPENES; INDOLE alkaloids; ALKALOIDS; STRYCHNOS; ALCOHOL dehydrogenase; PYRROLIZIDINES
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-00154-x