An efficient chemoenzymatic synthesis of dihydroartemisinic aldehyde

Demiray, Melodi, Tang, Xiaoping, Wirth, Thomas ORCID: https://orcid.org/0000-0002-8990-0667, Faraldos, Juan A. and Allemann, Rudolf K. ORCID: https://orcid.org/0000-0002-1323-8830 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
ISSN:	1433-7851
Funders:	BBSRC, EPSRC
Date of First Compliant Deposit:	22 March 2017
Date of Acceptance:	19 January 2017
Last Modified:	04 May 2024 01:26
URI:	https://orca.cardiff.ac.uk/id/eprint/99274

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