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An efficient chemoenzymatic synthesis of dihydroartemisinic aldehyde

Demiray, Melodi, Tang, Xiaoping, Wirth, Thomas, Faraldos, Juan A. and Allemann, Rudolf Konrad 2017. An efficient chemoenzymatic synthesis of dihydroartemisinic aldehyde. Angewandte Chemie - International Edition 56 (15) , pp. 4347-4350. 10.1002/anie.201609557

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Abstract

Artemisinin from the plant Artemisia annua is the most potent pharmaceutical for the treatment of malaria. In the plant, the sesquiterpene cyclase amorphadiene synthase, a cytochrome- dependent CYP450, and an aldehyde reductase convert farnesyl diphosphate (FDP) into dihydroartemisinic aldehyde (DHAAl), which is a key intermediate in the biosynthesis of artemisinin and a semisynthetic precursor for its chemical synthesis. Here, we report a chemoenzymatic process that is able to deliver DHAAl using only the sesquiterpene synthase from a carefully designed hydroxylated FDP derivative. This process, which reverses the natural order of cyclization of FDP and oxidation of the sesquiterpene hydrocarbon, provides a significant improvement in the synthesis of DHAAl and demonstrates the potential of substrate engineering in the terpene synthase mediated synthesis of highvalue natural products.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Uncontrolled Keywords: artemisinin; chemoenzymatic synthesis; sesquiterpenoids; substrate engineering; synthetic biology
Publisher: Wiley-Blackwell
ISSN: 1433-7851
Funders: BBSRC, EPSRC
Date of First Compliant Deposit: 22 March 2017
Date of Acceptance: 19 January 2017
Last Modified: 10 Oct 2017 21:46
URI: http://orca.cf.ac.uk/id/eprint/99274

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