“Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin” Westfall, P.J.; Pitera, D.J.; Lenihan, J.R.; Eng, D.; Woolard, F.X.; Regentin, R.; Horning, T.; Tsuruta, H.; Melis, D.J.; Owens, A.; Fickes, S.; Diola, D.; Benjamin, K.R.; Keasling, J.D.; Leavell, M.D.; McPhee, D.J.; Renninger, N.S.; Newman, J.D.; Paddon, C.J.
Proc. Natl. Acad. Sci. U.S.A. 2012,
109, E111-E118. DOI:
10.1073/pnas.1110740109.
Artemisia annua.
As a result, supplies of the drug are short, and those who need it often can’t afford it. The development of new processes for artemisinin production would therefore advance both public health and green chemistry interests. Total synthesis of the drug hasn’t been considered as a viable alternative because of
low yields, but a lot of effort has been directed toward developing semi-synthetic sources of artemisinin using a combination of microbial fermentation and chemical synthesis. Toward this end, the
Keasling lab reported a few years ago that they had constructed a
biosynthetic pathway for the artemisinin precursor amorpha-4,11-diene in yeast with yields of ~200 mg/L—already impressive given the complexity of the molecule.
Amorphadiene synthase (ADS) comes from
Artemisia annua; the rest of the genes are from yeast.
