Searching for Artemisinin Production Improvement in Plants and Microorganisms

Katarzyna      Barbacka; Wanda      Baer-Dubowska

Abstract

The endoperoxide sesquiterpene lactone artemisinin which is isolated from the plant Artemisia annua, and its semi-synthetic derivatives, are potent, novel, antimalarial drugs. They are effective against multidrug-resistant Plasmodium strains and have become essential components of the so-called Artemisinin-based Combination Therapy, that is recommended by the World Health Organization as the treatment of choice for malaria tropica. Moreover, artemisinin and its derivatives show additional anti-parasite, antitumor, and anti-viral properties. The plants, however, are very poor resources for the drug, as the content of artemisinin is low (from 0,1 to 1,5 % of dried leaves) and dependent on seasonal and somatic variations as well as the infestation of bacteria, fungi and insects. A chemical synthesis of the compound is complex and uneconomic. Therefore, artemisinin is in short supply and remains unaffordable for most people in malariaendemic countries. Thus, many researchers have focused on enhancing the production of artemisinin, first, through traditional breeding and in in vitro plant tissue cultures and, then, by heterologous expression systems (a semi-synthetic approach) with the use of genetically-modified or transgenic microbes. In this review, we summarize the progress made in the production of artemisinin by the biotechnological approach.

Keywords: Artemisinin, ACTs, biosynthesis, metabolic engineering, antimalarial drugs, biotechnological approach, anti-viral properties, sesquiterpenoid endoperoxide, protozoan parasites, malaria transmission, naphthaleneacetic acid, organic solvents, artemisinin pathway, high amorphadiene accumulation, hydrophobic n-dodecane