Malaria drug precursor made in yeast

The total synthesis of the antimalarial drug artemisinin (bottom) is difficult and expensive, but synthesizing it from its immediate biosynthetic precursor, artemisinic acid (top), could be a cost-effective approach to increasing supplies of the drug. Jay D. Keasling and coworkers at the University of California, Berkeley, have used a three-pronged approach to make yeast produce significant amounts (115 mg/L) of artemisinic acid (Nature 2006, 440, 940). First, they manipulated the yeast farnesyl pyrophosphate (FPP) biosynthetic pathway to increase production of FPP and prevent FPP from being used for sterol synthesis. Then they introduced a gene for amorphadiene synthase, which converts FPP to amorphadiene. Finally, they introduced a novel cytochrome P450 that performs a three-step oxidation of amorphadiene to artemisinic acid. The engineered yeast produced much more quickly an amount of artemisinic acid comparable to the amount produced by the plant that usually makes it. Additional work will be required to optimize the yield and scale up the process.