Advances in Sesquiterpene Synthases (Cyclases) of Artemisia annua

Artemisinin, a novel and highly potent antimalarial drug, is produced from the plant Artemisia annua L. with very low yields ranging from 0.01% to 0.8% on a dry-weight basis. This makes artemisinin an expensive drug. Several studies reported the chemical synthesis of artemisinin, but none of them seems to be a viable economical alternative compared with the isolation of artemisinin from the plant. Hence, a higher concentration of artemisinin in the plant is necessary for the cheap production of antimalarial drug. Several types of cyclic sesquiterpenes in Artemisia annua have been characterized so far, and each was derived from the common cyclic precursor FDP in a reaction catalyzed by a sesquiterpene synthase. Sesquiterpene synthases are widely regarded as the rate-determining regulatory enzymes in the pathways they participate in, and several sesquiterpene synthases have been cloned from Artemisia annua till date. This report gives a brief review of the following sesquiterpene synthases: epi-cedrol synthase, amorpha-4,11-diene synthase, β-caryophyllene synthase, (E)-β-farnesene synthase, germacrene A synthase, as well as a novel sesquiterpene synthase whose function remains largely unknown. This study provides a better understanding of the metabolic engineering of Artemisia annua.