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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.
