Biosynthesis of artemisinin – revisited

Abstract

Artemisinin is a well-known antimalarial drug isolated from the Artemisia annua plant. The biosynthesis of this well-known molecule has been reinvestigated by using [1-¹³C]acetate, [2-¹³C]acetate, and [1,6-¹³C₂]glucose. The ¹³C peak enrichment in artemisinin was observed in six and nine carbon atoms from [1-¹³C]acetate and [2-¹³C]acetate, respectively. The ¹³C NMR spectra of ¹³C-enriched artemisinin suggested that the mevalonic acid (MVA) pathway is the predominant route to biosynthesis of this sesquiterpene. On the other hand, the peak enrichment of five carbons of ¹³C-artemisinin including carbon atoms originating from methyls of dimethylallyl group of geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP) was observed from [1,6-¹³C₂]glucose. This suggested that GPP which is supposed to be biosynthesized in plastids travels from plastids to cytosol through the plastidial wall and combines with isopentenyl pyrophosphate (IPP) to form the (E,E)-FPP which finally cyclizes and oxidizes to artemisinin. In this way the DXP pathway also contributes to the biosynthesis of this sesquiterpene.

Keywords:

• Artemisia annua
• artemisinin
• biosynthesis
• sesquiterpene
• ¹³C-NMR
• mevalonic acid pathway (MVA)
• deoxyxylulose pyrophosphate pathway (DXP)

Acknowledgements

One of the authors (NS) is thankful to CSIR for Research Internship at CIMAP. Also, we are thankful to Director, CIMAP, for encouragement during the course of work. Our thanks are also due to Mr. M.R. Khan for helping us in maintaining the plants at CIMAP farm.