Issue: June 2018
April 26, 2018
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Researchers engineer shrub to produce more artemisinin

Issue: June 2018
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Researchers said they have engineered a Chinese shrub to produce more of the potent antimalarial compound artemisinin.

Tang Kexuan , PhD, professor of agriculture and biology at Jiao Tong University, and colleagues said their metabolically engineered line of Artemisia annua — or sweet wormwood — shrubs can produce high levels of artemisinin and are ready for large-scale production.

“Nearly half of the world’s population is at risk of malaria,” Tang said in a news release. “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.”

According to WHO, progress against malaria has stalled. There were approximately 216 million cases and 445,000 deaths from the mosquito-borne disease in 2016 despite an estimated $2.7 billion being spent on malaria control and elimination.

Tang Kexuan, PhD, and colleagues engineered lines of Artemisia annua to produce more of the antimalarial compound artemisinin.
Tang Kexuan, PhD, and colleagues engineered lines of Artemisia annua to produce more of the antimalarial compound artemisinin.
Source: Liu Ying, Shanghai Xinhua News Agency.

Artemisinin-based combination therapies, or ACTs, are recommended to treat uncomplicated malaria caused by Plasmodium falciparum — the most prevalent malaria parasite in Africa — and are considered by experts to be the most effective antimalarial medicines available. Their supply is reliant upon the agricultural production of A. annua, the only natural source of artemisinin in the world, according to Tang and colleagues. But production cannot always meet demand because artemisinin makes up 1% or less of the dry weight of A. annua leaves. Moreover, a semisynthetic system to produce artemisinin is costly and unable to replace natural production, they said.

Previous attempts to engineer A. annua to produce higher levels of artemisinin failed, but Tang and colleagues succeeded by assembling the shrub’s large and complex genomic sequence — a process that took several years. It is one of the few sequenced genomes in the Asteraceae family of plants. After assembling the genomic sequence, Tang and colleagues were able to identify ways to increase the artemisinin yield of the shrubs — generating lines wherein the compound equals 3.2% of the dry weight of the leaves, according to the news release.

According to the release, they sent seed samples of the engineered shrubs to Madagascar — the African country that grows the most A. annua — for a field trial. Their goal is to develop lines with leaves that contain 5% artemisinin.

"We hope our research can enhance the global supply of artemisinin and lower the price from the plant source," Tang said. "It is not expensive to generate high-level artemisinin lines. We have propagated hundreds of high artemisinin producer lines via cutting and selection and scaled up the production of these plants. Hopefully our high artemisinin transgenic lines will be grown at a massive scale next year." – by Gerard Gallagher

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Reference:

WHO. Global response to malaria at crossroads. 2017. http://www.who.int/en/news-room/detail/29-11-2017-global-response-to-malaria-at-crossroads. Accessed April 24, 2018.

Disclosures: The authors report no relevant financial disclosures.