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Title: Strategies for improving artemisinin content in the engineered Artemisia annua plant

Kexuan Tang

Shanghai Jiao Tong University, China

Biography

Dr. Kexuan Tang is the distinguished professor at Shanghai Jiao Tong University, China. He got Bachelor degree from Sichuan University in 1985, master degree from Beijing Agricultural University in 1988, and Ph.D degree supervised by Prof. Edward C. Cocking from University of Nottingham, UK in 1996. From 2007 to 2009, he did his postdoctoral research at John Innes Research Centre with Dr. Paul Christou and University of California-Davis with Dr. Pamela Ronald. He was awarded honorary doctorate by Linnaeus University, Sweden in 2012. He has published over 300 papers in SCI journals and has over 200 patents filed or granted.

Abstract

Artemisinin, an endoperoxide-containing sesquiterpene lactone isolated from Artemisia annua L., is extensively used in treating malaria. The artemisinin-based combination therapy (ACT) is recommended by World Health Organization (WHO) to combat the drug-resistant malaria. China's pharmacologist Youyou Tu received 2015 Nobel Prize in Physiology or Medicine due to the finding of artemisinin. However, the artemisinin content in A. annua is low (0.01-1% dry weight, DW), and the demand for artemisinin is huge (180-200 tons/year). In addition, although the artemisinin biosynthesis in A. annua is almost elucidated, how artemisinin biosynthesis is regulated is poorly known. Here, we report the development of multi metabolic engineering strategies to increase artemisinin content in A. annua. The strategies include over-expressing artemisinin biosynthetic pathway genes, downregulating the competitive pathway genes, indirect regulation, transcriptional regulation, increasing glandular trichome density and transporting strategy. Using these strategies, we have developed extremely high artemisinin content engineered A. annua lines in which the artemisinin content reached 2-3% (DW), which are in the field trial in Africa. In addition, we have identified and functionally characterized a number of transcription factors which can work alone or form the complex to regulate artemisinin biosynthesis and trichome initiation. These achievements, combined with efforts of the newly established Artemisinin Industrial Alliance comprised of all major Artemisia growers, artemisinin and ACT producers in China, will fundamentally solve the unstable artemisinin supply problem and guarantee the world the constant supply of artemisinin at low price to combat malaria.