Abstract
Artemisinin-based therapies are the only effective treatment for malaria, which reached to 219 million cases and killed 435,000 people in 2017. To meet the growing demand for artemisinin and make it accessible to the poorest, genetic engineering of Artemisia annua becomes one of the most promising approaches to improve artemisinin yield. In this work, AabZIP9 transcription factor has been identified and characterized. The expression profile of AabZIP9 revealed that it was clustered with the artemisinin specific biosynthetic pathway genes ADS, CYP71AV1, DBR2, and ALDH1. Furthermore, the transiently dual-LUC analysis showed that the activation of ADS promoter was enhanced by AabZIP9. Meanwhile, yeast one-hybrid assay showed that AabZIP9 was able to bind to the “ACGT” cis-element present in both ADS and CYP71AV1 promoters. AabZIP9 gene was driven by the constitutive CaMV35S promoter and the glandular trichome specific CYP71AV1 promoter and stably transformed into A. annua plants. The transcript level of AabZIP9 was increased in both of the 35S and CYP71AV1 driven transgenic plants compared with the wild type or GUS control plants. All the transgenic A. annua plants overexpressing AabZIP9 showed elevated transcript level of ADS, but the transcription levels of CYP71AV1, DBR2, and ALDH1 have no significant change in both types of transgenic plants. The significantly upregulated ADS promoted the accumulation of artemisinin, dihydroartemisinic acid, and artemisinic acid biosynthesis in the transgenic A. annua plants. These results suggest that AabZIP9 can positively regulate the biosynthesis of artemisinin.
Highlights
Malaria has been a pandemic disease, threatening people in tropical and subtropical regions of the world, compromising millions of lives
Since the biosynthesis of plant secondary metabolites is usually species or tissue specific (Goossens, 2014), to identify transcription factors involved in the regulation of artemisinin biosynthesis we looked at their expression across tissues
We identified several transcription factors (TFs) of the bZIP family which showed expression profiles similar to that of genes of the artemisinin biosynthetic pathway such as amorpha diene synthase (ADS), CYP71AV1, double bond reductase 2 (DBR2), and aldehyde dehydrogenase 1 (ALDH1) (Figure 1A and Supplementary Figure 1)
Summary
Malaria has been a pandemic disease, threatening people in tropical and subtropical regions of the world, compromising millions of lives. The WHO (World Health Organization) reported 219 million cases of malaria in 2017 and 435,000 deaths (WHO, 2018). Artemisinin, a secondary metabolite produced in the wild plant Artemisia annua, along with its derivatives is the main ingredient of artemisinin combination therapies (ACTs), which is currently the only effective cure for malaria (Okell et al, 2014). Youyou Tu, who was further awarded the Nobel Prize in Physiology and Medicine in 2015, could significantly elevate the current antimalaria therapies and save millions of lives. In addition to antimalarial activity and due to its diverse promising functions, including anticancer (Tin et al, 2012), viral (Obeid et al, 2013), AabZIP9 Regulates Artemisinin Biosynthesis inflammatory (Chadwick et al, 2013), diabetic (Li et al, 2017), and tuberculosis therapies (Zheng et al, 2017), the demand for artemisinin has risen in the recent years
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
