Engineered Chinese shrub produces high levels of antimalarial compound

Artemisinin is a potent antimalarial compound produced naturally by the Chinese shrub Artemisia annua, commonly known as sweet wormwood. Currently,however, the low amount of artemisinin produced in the leaves of this plant does not meet the global demand. 

The best available treatment for malaria, particularly for cases caused by P. falciparum, is artemisinin-based combination therapy. In addition to its antimalarial activity, therapeutic effects of artemisinin have been reported for cancer, tuberculosis, and diabetes. However, the supply of artemisinin is limited because this medicinal compound typically makes up only 0.1%-1.0% of the dry weight of A. annua leaves.

Researchers in China report a high-quality draft genome sequence of A. annua and their use of this information along with gene expression data to metabolically engineer plant lines that produce high levels of artemisinin.

"Nearly half of the world's population is at risk of malaria," says senior study author Kexuan Tang of Shanghai Jiao Tong University. "Our strategy for the large-scale production of artemisinin will meet the increasing demand for this medicinal compound and help address this global health problem." Tang and his collaborators generated a high-quality draft assembly of the 1.74 gigabase A. annua genome, which contains 63,226 protein-coding genes, one of the largest numbers among sequenced plant species. It took several years to complete the genome sequence due to its large size and high complexity.

Based on the genomic and transcriptomic data, the researchers identified novel genes involved in regulating artemisinin biosynthesis. By simultaneously increasing the activity of three genes: HMGR, FPS, and DBR2, spanning the entire artemisinin biosynthetic pathway, the researchers generated A. annua lines that produced high artemisinin levels – 3.2% of the dry weight of the leaves.