The Biosynthesis of Artemisinin
Description: Malaria is currently responsible for one-two million deaths every year. Artemisinin is an antimalarial drug derived from the medicinal plant Artemisia annua. Because of increasing resistance to conventional malarial therapies, artemisinin is now the only drug which can treat the often fatal condition of cerebral malaria in many parts of the World. Artemisinin is produced on a multi-ton scale entirely from the plant source by pharmaceutical factories in China and Vietnam. Recently, there have been problems with both the cost and the supply of artemisinin. The most attractive approaches to address these issues are: i) to increase the yield of this antimalarial drug from the parent plant, A. annua, via a crop-breeding program; and, ii) to genetically engineer the pathway to artemisinin within a microbial host, in order to permit its production by fermentation. A complete understanding of the biosynthetic route to artemisinin, in which all of the biosynthetic intermediates have been unambiguously identified, is clearly the foundation of both approaches, since this provides the most secure basis on which to search for the relevant enzymes in that pathway. Surprisingly, however, the complete sequence of intermediates which are involved in the biosynthesis of this vitally important natural product has never been fully established. The aim of this proposal is to fill in the gaps in our knowledge of the biosynthetic pathway to artemisinin in A. annua by means of rigorous feeding experiments, involving labelled precursors, which will be produced by chemical synthesis. Particular emphasis will be placed on the later steps in the pathway, which are the least well understood.
Amount: £387,600
Funding type: research
Start date: 2009-06-07
End date: 2012-12-07
Funded outputs count: 4
Funder award ID: BB/G008744/1
OpenAlex ID: G6931796420