Monday, July 27, 2009 - 9:30 AM
S26

Microbially-derived Semi-Synthetic Artemisinin: Synthetic Biology for the production of artemisinin, a component of potent antimalarial combination therapies

Patrick J. Westfall1, Chris Paddon1, Rika Regentin1, Jay D. Keasling2, and Jack Newman1. (1) Amyris Biotechnologies, 5885 Hollis Street, Suite 100, Emeryville, CA 94608, (2) Departments of Chemical Engineering and Bioengineering, UC-Berkeley; Lawrence Berkeley National Laboratory, EmeryStationEast, 5885 Hollis St, 4th floor, Emeryville, CA 94608

There are estimated to be 350-500 million clinical episodes of malaria annually, caused by the Plasmodium parasite, with more than 1 million deaths, the highest mortality occurring in children under 5 years of age.  Traditional drug treatments have become ineffective as P. falciparum has become resistant to almost all currently used drug therapies.  Exceptions to the pattern of clinical drug resistance are artemisinin-based combination therapies (ACTs), which are potent antimalarials.  Artemisinin is currently extracted from the plant Artemisia annua, but an additional semi-synthetic source would be advantageous to meet anticipated demand, stabilize the market, lower costs and increase availability of ACTs.    We are developing a fermentation process to produce artemisinin precursors in microbes, with subsequent chemical conversion to artemisinin.   The use of synthetic biology to develop strains of Escherichia coli and Saccharomyces cerevisiae for the production of the artemisinin precursors amorphadiene and artemisinic acid will be described, along with process development to produce significant quantities of amorphadiene.  Production of artemisinin precursors by fermentation followed by chemical conversion to artemisinin may allow for the development of a process that would provide an alternative source of artemisinin that could then be incorporated into ACTs.  Additional uses of synthetic biology for the production of industrially relevant products will also be summarized.