Impact of integrated omics technologies for identification of key genes and enhanced artemisinin production in Artemisia annua L

Abstract

Medicinal plants are the source of an enormous variety of bioactive secondary metabolites and have potential synergistic effects against a broad range of human diseases. According to the World Health Organization (WHO), more than 80% of the world’s population depend on medicinal plants for everyday healthcare. One of the most popular secondary metabolites with immense 222therapeutic potential is artemisinin (AN), present in a well-known Asteraceae family member, Artemisia annua L. The AN isolated from the leaves of A. annua by Chinese scientist You You Tu is acknowledged as an effective antimalarial compound (Barbacka and Baer-Dubowska 2011). AN and its bioactive derivatives isolated from A. annua are powerful medicines widely used for their ability to swiftly control Plasmodium malaria. AN-based combination therapies (ACTs), with their established safety record, are the first line of treatment recommended by WHO (2014) for malaria caused by Plasmodium falciparum. In addition to its antimalarial effects, AN has recently been evaluated for its potential antibacterial, antiviral, antitumor, antileishmanial, antischistosomiatic, anti-sleeping sickness, anticancer, and herbicidal properties (Efferth et al. 2011; Utzinger et al. 2001; Sen et al. 2007; Mishina et al. 2007). However, the low content of AN in plant tissue has resulted in poor yield/production of AN, which seems insufficient to fulfill the demand for 392 million courses of ACT each year (WHO 2014). Semisynthetic derivatives of AN, such as artemether and artesunate, are also commonly produced commercially, but they are not routinely available in remote rural areas. Moreover, these derivatives are very expensive, and low yields of AN result in relatively high costs for its extraction and purification. Further, A. annua requires a relatively long period of time for its agricultural cultivation, which results in wide swings in affordable, best-quality, robust supply of raw materials, and prices. Intensified efforts have been carried out to increase AN production (Liu et al. 2006). However, the routine metabolic engineering strategy, via overexpressing or downregulating key genes in AN biosynthetic pathways, has not proved very effective. Glandular secretory trichomes, sites of AN biosynthesis on the surface of A. annua, are the new target for increasing AN yield (Duke et al. 1994). In general, the population and morphology of glandular secretory trichomes in A. annua (AaGSTs) are positively correlated with AN content. Higher production of AN requires breeding of A. annua to optimize the biomass yield and trichome density. Various efforts have been made to breed high-trichome density cultivars of the plant for increased AN production. However, various approaches have been already taken into consideration for the semisynthesis of AN (Paddon et al. 2013). The production of AN is also challenging because A. annua remains relatively undeveloped as a crop. Therefore, there is a need to improve the varieties and cultivation strategies of A. annua for farmers in developing countries, because this would bring immediate benefits to the existing supply chain of AN. Major advancements in omics technologies such as genomics, proteomics, and metabolomics have enabled high-throughput monitoring of a variety of molecular and biochemical processes. These techniques have been widely applied to identify biological variants and complex biochemical pathways/systems. Many omics platforms target the comprehensive analysis of genes (genomics), mRNA (transcriptomics), proteins (proteomics), and metabolites (metabolomics). However, the interpretation of obtained data is challenging due to very complex biochemical and metabolic pathways.223. © 2018 by Taylor & Francis Group, LLC.