An Efficient Chemoenzymatic Synthesis of Dihydroartemisinic Aldehyde

نویسندگان

  • Melodi Demiray
  • Xiaoping Tang
  • Thomas Wirth
  • Juan A. Faraldos
  • Rudolf K. Allemann
چکیده

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.

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عنوان ژورنال:

دوره 56  شماره 

صفحات  -

تاریخ انتشار 2017