Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00154-x
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Funding
- European Research Council [311363]
- BBSRC [BB/J004561/1]
- Region Centre-Val de Loire, France (ABISAL grant)
- Region Centre-Val de Loire, France (BioPROPHARM project) [ARD2020]
- DFG [FR 3720/1-1]
- EMBO Long trem Fellowship [ALTF 239-2015]
- BBSRC [BBS/E/J/000CA512, BB/N007905/1, BBS/E/J/000PR9790] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/N007905/1, BBS/E/J/000CA512, BBS/E/J/000PR9790] Funding Source: researchfish
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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-beta-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.
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