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June 23, 2011 | By:  Eric Sawyer
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Artemisinin: A Synthetic Biology Success Story

UPDATE (June 27, 2014): I receive more correspondence on this story than any other! You can find a much more detailed post about artemisinin here. The post is from 2012. If you aren't satisfied by that, tweet at me (@ericmsawyer) to persuade me to make a new, up-to-date post.

In 2003, Jay Keasling and his team at UC Berkeley announced initial success in an endeavor that has since become "the" poster child success story of synthetic biology. They had successfully implanted genes into E. coli that are part of a metabolic pathway that produces a precursor to the antimalarial drug artemisinin. They would go on to engineer the entire pathway into yeast with multimillion dollar financial support from the Bill and Melinda Gates Foundation. It is much cheaper to use yeast to produce the precursor and then convert it to artemisinin than it is to synthesize artemisinin outside of living cells.

According to the World Health Organization (WHO), there were 247 million cases of malaria in 2008 alone. The same year almost one million sufferers perished from the illness. The malaria parasite is spread by mosquitos, and those residing within tropical climates are particularly at risk (the red areas in the map). Though the disease can be treated with antimalarial drugs, there is

limited access to medical care in the poorest of the affected regions. On top of that, many populations of the parasite have evolved resistance to the popular drugs chloroquine and sulfacoxine-pyrimethamine. Artemisinin has not been met with widespread parasite resistance, and WHO warns that if such resistance developed "the public health consequences could be dire, as no alternative antimalarial medicines will be available in the near future." Clearly artemisinin is a key player in our arsenal against this disease.

In nature, artemisinin is produced by the plant Artemisia annua (see picture). The global supply of artemisinin comes almost exclusively from farmers that cultivate the plant. However, the global supply of artemisinin is highly volatile because of the uncertainty associated with crop success. Keasling and his team wanted to provide a cheap and reliable alternative to agricultural production. This required engineering an entire non-native metabolic pathway into yeast cells. "Metabolic engineering" is becoming a real buzz word in synthetic biology. Craig Venter, for instance, is working to develop bioreactors in which algae cells convert carbon dioxide from the atmosphere into fuel. Whether in the areas of medicine, energy, environment, or something else, the applications of this technology are of immense importance. The attention garnered by Keasling's achievements even secured him a spot as Discover Magazine's scientist of the year in 2006, the year he reported that the entire pathway had been constructed in yeast.

At this point it isn't clear exactly what benefits we will reap from metabolic engineering technologies in the near future. Noorden (2010) reports that the price of artemisinin coming out of traditional agriculture has fallen so much that producing it in a bioreactor would not lower the cost as initially anticipated. However all is not lost as the new technology can pick up the slack during bad crop years. It is also worth noting that this advance is, quite possibly, only the tip of the iceberg when it comes to metabolic engineering. As our knowledge of biology and techniques for engineering it advance, I believe we might see considerable changes in industries like drug manufacturing, food production, and energy generation. Cells really are little factories, and they are amazingly efficient at what they do.

Image Credits: Mosquito: CDC (via Wikimedia); Map: Petaholmes (via Wikimedia); A. annua: Kristian Peters (via Wikimedia)

References and Further Reading:

Noorden, R. V. Demand for Malaria Drug Soars . Nature 466, 672–673 (2010).

Specter, M. "A Life of Its Own: Where Will Synthetic Biology Lead Us?" The New Yorker. September 28, 2009.

WHO. Malaria Fact Sheet.

Zimmer, C. "Scientist of the Year: Jay Keasling." Discover. Published online November 22, 2006.

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