Genetic engineering of artemisinin biosynthesis: prospects to improve its production

Artemisinin, a potent antimalarial natural compound, is obtained from aerial parts of Artemisia annua L. plants. The demand (101-119 MT) for artemisinin is exponentially increasing every year because of increased incidence of drug-resistant malaria throughout the world, especially in Africa and Asia. However, the presence of low concentrations (0.01-1.1 %) of the compound in A. annua L. plants poses a major constraint in the commercialization of artemisinin-based combination therapies (ACTs) recommended by WHO for the treatment of multidrug- resistant and cerebral malaria. Further, the improvement in the yield of artemisinin through conventional breeding, in vitro culture, cell suspension culture and total organic synthesis still poses a challenge. However, possibilities are there to enhance the artemisinin biosynthesis either by overexpression of the genes encoding enzymes associated with the rate-limiting steps of the mevalonate and artemisinin biosynthetic pathways or by the suppression of genes encoding enzymes of other competing pathways. Based on the current understanding of the pathway and cloning of the related genes, efforts have been made for the past few years to increase the artemisinin content in A. annua L., Cichorium intybus L. and microbes through metabolic engineering. In the present review, we have discussed the metabolic engineering strategies in both plant and microbial systems for artemisinin accumulation in bioengineered hosts.