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April 13, 2006
DRUG SYNTHESIS
Yeast Produce Malaria Drug Precursor
Researchers hope route will lead to a cost-effective approach to increasing supplies of artemisinin
Celia Henry Arnaud
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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.
Chemical engineering professor Jay D. Keasling and coworkers at the University of California, Berkeley, have engineered yeast to produce significant amounts (115 mg/L) of artemisinic acid (Nature 2006, 440, 940). They engineered the yeast in three steps. First, they manipulated the 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 that is comparable with the amount produced by the plant that usually makes it. Additional work will be required to optimize the yield and scale up the process.
- Chemical & Engineering News
- ISSN 0009-2347
- Copyright © 2006 American Chemical Society
