Abstract
Malaria is still an eminent threat to major parts of the world population mainly in sub-Saharan Africa. Researchers around the world continuously seek novel solutions to either eliminate or treat the disease. Artemisinin, isolated from the Chinese medicinal herb Artemisia annua, is the active ingredient in artemisinin-based combination therapies used to treat the disease. However, naturally artemisinin is produced in small quantities, which leads to a shortage of global supply. Due to its complex structure, it is difficult chemically synthesize. Thus to date, A. annua remains as the main commercial source of artemisinin. Current advances in genetic and metabolic engineering drives to more diverse approaches and developments on improving in planta production of artemisinin, both in A. annua and in other plants. In this review, we describe efforts in bioengineering to obtain a higher production of artemisinin in A. annua and stable heterologous in planta systems. The current progress and advancements provides hope for significantly improved production in plants.
Highlights
Malaria is still a global concern with around 214 million annual cases and 430,000 annual deaths, mainly among of children younger than 5 (World Health Organization [WHO], 2016). This fatal disease is caused by Plasmodium sp. Plasmodium falciparum that proliferate in female Anopheles mosquitoes (Cox, 2010)
The current preferred therapy is artemisinin combination therapy (ACT) (Banek et al, 2014; Lalloo et al, 2016) that is based on artemisinin produced in the natural source Artemisia annua
Efforts in plant breeding have been challenging due to the heterozygous nature of A. annua, which results in transgenic plants with varying degrees of artemisinin content even though they were generated in the same laboratory (Delabays et al, 2001; Graham et al, 2010; Larson et al, 2013)
Summary
Malaria is still a global concern with around 214 million annual cases and 430,000 annual deaths, mainly among of children younger than 5 (World Health Organization [WHO], 2016). Efforts in plant breeding have been challenging due to the heterozygous nature of A. annua, which results in transgenic plants with varying degrees of artemisinin content even though they were generated in the same laboratory (Delabays et al, 2001; Graham et al, 2010; Larson et al, 2013) This variation is due to the segregation of the heterozygous wild type progeny leading to a different genetic background than the parent plant. Treatments with elicitors such as methyl jasmonate has significantly increased artemisinin production by up to 49% including up-regulating the expression of artemisinin biosynthesis genes as well as increased GT index (0.128) (Baldi and Dixit, 2008; Wang et al, 2010; Dangash et al, 2014; Xiang et al, 2015). The progress and recent bioengineering advances in artemisinin production in stable heterologous in planta systems including genetic modifications of A. annua is summarized
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