Researchers close in on making a natural malaria drug.

Westfall, PJ, DJ Pitera, JR Lenihan, D Eng, FX Woolard, R Regentin, T Horning, H Tsuruta, DJ Melis, A Owens, S Fickes, D Diola, KR Benjamin, JD Keasling, MD Leavell, DJ McPhee, NS Renninger, JD Newman and CJ Paddon. 2012. Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proceedings of the National Academy of Sciences http://dx.doi.org/10.1073/pnas.1110740109.

Synopsis by Jean-Philip Lumb

A new approach to making the natural malaria drug artemisinin will increase supply and avoid the chemical steps now used to extract the drug from plants. The drug is meant to replace medicines that no longer control the malaria parasite spread by mosquitoes.

An affordable treatment for malaria is closer thanks to a process using both biology and chemistry to make artemisinin – an effective drug currently extracted from plants.

The method bypasses plants as the source of the drug. Instead, modified yeast change sugar into an advanced chemical that can be converted into artemisinin. Skirting plants decreases the cost, increases supply and avoids chemical extractions. A team of industrial and academic researchers in Berkeley, Calif., developed the biochemical route to the drug.

The process provides an alternative to traditional extractive procedures and highlights the increasing use of biotechnology in greener drug manufacturing.

Globally, the mosquito-borne infectious disease claims nearly 1 million lives per year. Health organizations estimate that 300 – 500 million people are infected on an annual basis, a population based primarily of children in Africa and Asia.

New medicines are needed because the current drugs do not work as well as they once did and controlling mosquitoes with insecticides – such as DDT – can harm the environment and human health.

Artemisinin is a desirable substitute to the widely used chloroquine-based antimalarial drugs. The Plasmodium parasite that causes malaria has become resistant to these traditional drugs.

While faster acting and more effective, artemisinin is expensive and supplies are often limited. Artemisinin is currently extracted from plants. Unfortunately, the extraction makes large-scale production too costly for countries where the drug is needed most. The methods also employ volatile organic solvents that levy a heavy environmental toll.

To overcome the current limitations in supply, a consortium of industry and academic researchers in California developed a new strain of yeast that can convert glucose into an artemisinin precursor. Standard organic chemistry practices are used for the remaining steps of the drug’s synthesis.

The combined biotechnology/synthetic chemistry approach promises to be an effective alternative to the extraction techniques currently in use. The cost is estimated as low as 300 million cures at 50 cents a treatment. A recent press-release, issued on the Amyris website, announced a partnership between Amyris, The Institute for OneWorld Health and Sanofi-Aventis to make doses of artemisinin available later this year.

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