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: | 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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