Artemisinin - From Traditional Chinese Medicine to Artemisinin Combination Therapies; Four Decades of Research on the Biochemistry, Physiology, and Breeding of Artemisia annua

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About this Research Topic

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Background

Artemisinin, the world’s most vital antimalarial drug, is a sesquiterpene lactone produced in specialized 10-celled glandular trichomes present on the leaves, stems and inflorescences of Artemisia annua, an annual herb from the genus Asteraceae. Over the past four decades research into A. annua has combined the work of many scientists across different disciplines from breeders to natural product chemists and geneticists. This work has led to the further understanding and development of A. annua into a crop for commercial artemisinin production to meet global demand.

The traditional breeding of A. annua alongside modern molecular breeding techniques have led to the development of good agronomic practices for cultivation of A. annua as a commercial crop and the creation of hybrids that accumulate artemisinin at greater than 1% leaf dry weight and maximum yields greater than 50 kg/ha. Transgenic approaches utilizing the knowledge gained from research into transcriptional regulation of the artemisinin pathway have also been investigated as a means of improving artemisinin production in planta. Studies into the physiology of A. annua have also revealed a number of important endogenous and environmental factors that influence artemisinin production and glandular trichome development. Such findings may lead to further improvements in A. annua for commercial artemisinin production.

The biochemical pathways leading to the biosynthesis of artemisinin precursors and the final steps of artemisinin formation in the glandular trichomes of A. annua have also been fully elucidated. This work has enabled synthetic biologists to transfer the pathway into the yeast, Saccharomyces cereviseae, paving the way to semi-synthetic production of remarkable yields of artemisinic acid, which then needs to undergo photochemical conversion into artemisinin. However, semi-synthetic production of artemisinin has not been successful commercially, principally due to cost of production. Some effort has also been put into artemisinin production in heterologous plant systems such as Nicotiana benthamiana, Nicotiana tabacum and even species of moss, but all with limited success so far. A. annua therefore remains the principal commercial platform for the production of artemisinin worldwide.

Relatively little effort has been put into understanding the in planta function of artemisinin. There is clear evidence for phytotoxicity of artemsinin produced by A. annua, therefore involvement in allelopathy and anti-herbivory have been postulated for this sesquiterpene lactone. Known anti-fungal and anti-microbial activities of artemisinin might also contribute to protection against pathogen attack on the A. annua plant.

This Research topic welcomes submissions of all types of articles, with a preference for original research, reviews, mini reviews, and opinions, addressing the following areas:

1) Phytochemistry of A. annua
2) Biochemistry of artemisinin biosynthesis in A. annua and transcriptional regulation of the artemisinin pathway,
3) A. annua physiology and phytohormonal regulation of trichome development on A. annua ,
4) Traditional / molecular breeding of high artemisinin yielding varieties of A. annua and transgenic approaches to enhance artemisinin production and/or alter the terpenoid profile of A. annua,
5) Environmental and post-harvest handling effects on the production of artemisinin in A. annua,
6) Ecological roles of artemisinin,
7) Plant and microbial heterologous systems for artemisinin production,

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Keywords: Artemisia annua, artemisinin, plant physiology, phytochemistry, glandular secretory trichomes, plant breeding, heterologous systems

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