Microbially Derived Artemisinin: A Biotechnology Solution to the Global Problem of Access to Affordable Antimalarial Drugs

Abstract

Despite considerable efforts by multiple governmental and nongovernmental organizations to increase access to artemisinin-based combination therapies (ACTs), these life-saving antimalarial drugs remain largely unaffordable to the most vulnerable populations. The cost of artemisinin derivatives, ACTs' crucial active ingredients, contributes significantly to the high price of these therapies. With a grant from the Bill and Melinda Gates Foundation, a partnership between Amyris Biotechnologies, the Institute for OneWorld Health, and the University of California, Berkeley is using synthetic biology to help reduce the cost of artemisinin. This article presents a description of the technological platform the partnership--called the Artemisinin Project--is developing to manufacture a low-cost, semi-synthetic artemisinin through a fermentation process. By making life-saving ACTs affordable to the people who most need them, the Artemisinin Project hopes to show that the power of biotechnology can be harnessed to provide solutions to global health problems.

Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin

“…In recent years there have been large fluctuations in the price and availability of ACTs (4), and in 2007-2008 less than 15% of children under five years of age with fever received ACTs in 11 out of 13 countries surveyed (5). There is an urgent need to increase the supply of artemisinin to both stabilize the price and increase the availability of ACTs in the developing world, but a significant increase in the cultivation of A. annua would be needed to satisfy projected global demand (6). Chemical synthesis of artemisinin is not economically feasible because of the complexity and low yield of the process (7), however semisynthesis of artemisinin following microbial production of a precursor molecule may be feasible (6).…”

“…There is an urgent need to increase the supply of artemisinin to both stabilize the price and increase the availability of ACTs in the developing world, but a significant increase in the cultivation of A. annua would be needed to satisfy projected global demand (6). Chemical synthesis of artemisinin is not economically feasible because of the complexity and low yield of the process (7), however semisynthesis of artemisinin following microbial production of a precursor molecule may be feasible (6). This report describes progress toward the production of semisynthetic artemisinin.…”

Conversion of Biomass into Bioplastics and Their Potential Environmental Impacts

“…One of the notable examples of SB derived biological circuits is the design of a metabolic pathway to produce a precursor of the anti-malaria compound Artemisinin, naturally found in the wormwood plant (Artemisia annua). The design and construction of this plant derived compound in engineered microbes, showed off the state of the art of enhanced metabolic engineering via SB (Hale et al, 2007;Keasling, 2008;Martin et al, 2003). A handful of successful circuits have been constructed to convert biomass to fuels and chemicals (Table 2).…”

Predicting Global Fund grant disbursements for procurement of artemisinin-based combination therapies

“…Accurate forecasting of demand is critical for ACT, because the key ingredient, artemisinin, is a natural product derived from a plant, creating supply chain challenges [9]. Production of an ACT requires 12 to 24 months from the planting of Artemisia annua to ACT production [4].…”