Artemisinin, a novel antimalarial drug: biochemical and molecular approaches for enhanced production.
Artemisinin, a sesquiterpene lactone containing an endoperoxide bridge, has been isolated from the aerial parts of Artemisia annua L. plants. It is effective against both drug-resistant and cerebral malaria-causing strains of Plasmodium falciparum. The relatively low yield (0.01-0.8 %) of artemisinin in A. annua is a serious limitation to the commercialization of the drug. Therefore, the enhanced production of artemisinin either in cell/tissue culture or in the whole plant of A. annua is highly desirable. It can be achieved by a better understanding of the biochemical pathway leading to the synthesis of artemisinin and its regulation by both exogenous and endogenous factors. Furthermore, genetic engineering tools can be employed to overexpress gene(s) coding for enzyme(s) associated with the rate limiting step(s) of artemisinin biosynthesis or to inhibit the enzyme(s) of other pathway competing for its precursors. These aspects which may be employed to enhance the yield of artemisinin both in vitro and in vivo are discussed in this review.
Abdin
M Z
MZ
Centre for Biotechnology, Faculty of Science, Hamdard University, New Delhi, India. mzabdin@rediffmail.com
Israr
M
M
Rehman
R U
RU
Jain
S K
SK
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D031172:Artemisia annua; D037621:Artemisinins / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D005818:Genetic Engineering; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000188:drug therapy; D008517:Phytotherapy; D028321:Plant Preparations / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D007783:Lactones; D028321:Plant Preparations; D012717:Sesquiterpenes; C031327:artemisinin