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Yeast Synthetic Biology for Production of Artemisinin as an Antimalarial Drug

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Synthetic Biology of Yeasts

Abstract

Artemisinin, a sesquiterpene endoperoxide lactone derived from Artemisia annua, is highly effective against malaria parasite Plasmodium falciparum. Artemisinin and its derivatives (collectively termed artemisinins) demonstrate additional anticancer, anti-inflammation, antiviral, and anti-SARS-CoV-2 activity. Because of the expensive medicine of artemisinins and the low content of artemisinin biosynthesis in native host, researchers have been endeavored to produce artemisinin via alternative approaches. Previous attempts give attention to increase artemisinin biosynthesis via common plant breeding techniques and on engineering cultivated plants for wide production. However, current trends are focusing on the bioengineering of artemisinin biosynthetic pathway in heterologous expression platforms. To date, in planta artemisinin production in two model plants, tobacco (Nicotiana benthamiana) and moss (Physcomitrella patens), has been reported successfully. Nevertheless, to meet the large-scale demands, de novo reconstituting of artemisinin biosynthetic pathway in heterologous microorganisms such as Escherichia coli and Saccharomyces cerevisiae has had documentary achievements. Since there are challenges for the expression of cytochrome P450s (CYPs) from the eukaryotic origin (such as CYP71AV1) in E. coli, S. cerevisiae has been proposed as a heterologous host for production of artemisinin precursors such as amorphadiene, artemisinic acid, and dihydro artemisinic acid. Moreover, the presence of the MVA biosynthetic pathway for production of universal sesquiterpenes precursor, farnesyl pyrophosphate (FPP), and relative compatibility of S. cerevisiae cell environment for the expression of plant-origin genes (enzymes) have made this microorganism as a favorable platform for artemisinins production.

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Correspondence to Arman Beyraghdar Kashkooli .

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Beyraghdar Kashkooli, A., Farmanpour-Kalalagh, K., Babaei, A. (2022). Yeast Synthetic Biology for Production of Artemisinin as an Antimalarial Drug. In: Darvishi Harzevili, F. (eds) Synthetic Biology of Yeasts. Springer, Cham. https://doi.org/10.1007/978-3-030-89680-5_6

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