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An Efficient Chemoenzymatic Synthesis of Dihydroartemisinic Aldehyde.

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 high-value natural products.

SUBMITTER: Demiray M

PROVIDER: S-EPMC5396139 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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An Efficient Chemoenzymatic Synthesis of Dihydroartemisinic Aldehyde.

Demiray Melodi M Tang Xiaoping X Wirth Thomas T Faraldos Juan A JA Allemann Rudolf K RK

Angewandte Chemie (International ed. in English) 20170313 15

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 usin ...[more]

PMID: 28294491

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