Developing Artemisia annua for the extraction of artemisinin to treat multi-drug resistant malaria

Semi-synthetic derivatives of the sesquiterpene artemisinin have worldwide become the main treatment for P. falciparum malaria. Artemisinin-combination therapies (ACTs), containing artemether or artesunate combined with non-isoprenoid drugs, are recommended as first line treatment by the World Health Organization, particularly in areas where resistance against quinine and quinine analogues has developed.

Whereas methods for the total synthesis of artemisinin have been developed, artemisinin extracted from the leaves of Artemisia annua L. (Asteraceae) is still the preferred source for commercial production of antimalarial drugs.

The biosynthetic pathway of artemisinin is well-known and a number of genes that regulate artemisinin biosynthesis have been identified. Various attempts have been made to enhance the yield of artemisinin in crops or plant cell cultures through the use of genetic engineering. Another approach has been semi-synthesis of artemisinin via artemisinic acid in genetically engineered yeast.

Although genetic engineering holds a great promise for the future, currently the largest improvements in artemisinin yield have been obtained through creation of high-yielding varieties by classical breeding programs combined with modern agricultural production techniques.