The stacked over-expression of FPS, CYP71AV1 and CPR genes leads to the increase of artemisinin level in Artemisia annua L.

Chen, Yunfei; Shen, Qian; Wang, Yueyue; Wang, Tao; Wu, Shaoyan; Zhang, Ling; Lu, Xu; Zhang, Fangyuan; Jiang, Weimin; Qiu, Bo; Gao, Erdi; Sun, Xiaofen; Tang, Kexuan

doi:10.1007/s11816-012-0262-z

Cited by 31 publications

(12 citation statements)

References 35 publications

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“…Overexpression of several genes responsible for key steps of artemisinin biosynthesis, such as farnesyl pyrophosphate synthase (FPS), ADS, CYP71AV1, CPR, and DBR2 led to approximately a double increase of artemisinin production [265][266][267].…”

Section: Artemisininmentioning

confidence: 99%

“…Based on these conclusions, many research groups focused their interest in co-overexpressing two or more genes in A. annua to further increase the amount of artemisinin [262,263]. For example, co-overexpression of FPS, CYP71AV1, and CPR genes increased the artemisinin content by 3.6 fold (2.9 mg/g fw) in comparison with control plants [267], and the simultaneous overexpression of ADS, CYP71AV1, and CPR resulted in 2.4-fold increase of artemisinin (15.1 mg/g DW) compared to control plants [268].…”

Section: Artemisininmentioning

confidence: 99%

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The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants

et al. 2018

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Plants have always been used as medicines since ancient times to treat diseases. The knowledge around the active components of herbal preparations has remained nevertheless fragmentary: the biosynthetic pathways of many secondary metabolites of pharmacological importance have been clarified only in a few species, while the chemodiversity present in many medicinal plants has remained largely unexplored. Despite the advancements of synthetic biology for production of medicinal compounds in heterologous hosts, the native plant species are often the most reliable and economic source for their production. It thus becomes fundamental to investigate the metabolic composition of medicinal plants to characterize their natural metabolic diversity and to define the biosynthetic routes of important compounds to develop strategies to further increase their content. We present here a number of case studies for selected classes of secondary metabolites and we review their health benefits and the historical developments in their structural elucidation and characterization of biosynthetic genes. We cover the cases of benzoisoquinoline and monoterpenoid indole alkaloids, cannabinoids, caffeine, ginsenosides, withanolides, artemisinin, and taxol; we show how the "early" biochemical or the more recent integrative approaches-based on omics-analyses-have helped to elucidate their metabolic pathways and cellular compartmentation. We also summarize how the knowledge generated about their biosynthesis has been used to develop metabolic engineering strategies in heterologous and native hosts. We conclude that following the advent of novel, high-throughput and cost-effective analytical technologies, the secondary metabolism of medicinal plants can now be examined under the lens of systems biology.

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Section: Artemisininmentioning

confidence: 99%

Section: Artemisininmentioning

confidence: 99%

The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants

et al. 2018

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“…The samples were then injected into a Waters Alliance 2695 HPLC system coupled with a Waters 2420 ELSD detector (Milford, MA, USA) using pure artemisinin as standard (sigma). The HPLC condition was as described previously (Chen et al, 2012). Three biological repeats were applied for each sample.…”

Section: Artemisinin Content Analysis By Hplc-elsdmentioning

confidence: 99%

AaABCG40 Enhances Artemisinin Content and Modulates Drought Tolerance in Artemisia annua

Liu

Hassani

et al. 2020

Front. Plant Sci.

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The phytohormone Abscisic acid (ABA) regulates plant growth, development, and responses to abiotic stresses, including senescence, seed germination, cold stress and drought. Several kinds of researches indicate that exogenous ABA can enhance artemisinin content in A. annua. Some transcription factors related to ABA signaling are identified to increase artemisinin accumulation through activating the artemisinin synthase genes. However, no prior study on ABA transporter has been performed in A. annua. Here, we identified a pleiotropic drug resistance (PDR) transporter gene AaPDR4/ AaABCG40 from A. annua. AaABCG40 was expressed mainly in roots, leaves, buds, and trichomes. GUS activity is primarily observed in roots and the vascular tissues of young leaves in proAaABCG40: GUS transgenic A. annua plants. When AaABCG40 was transferred into yeast AD12345678, yeasts expressing AaABCG40 accumulated more ABA than the control. The AaABCG40 overexpressing plants showed higher artemisinin content and stronger drought tolerance. Besides, the expression of CYP71AV1 in OE-AaABCG40 plants showed more sensitivity to exogenous ABA than that in both wild-type and iAaABCG40 plants. According to these results, they strongly suggest that AaABCG40 is involved in ABA transport in A. annua.

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“…Overexpression of key terpenoid genes encoding for the enzymes IDI, FPS, HMGR, the plastid targeted DXR and HDR have increased production significantly (some by 2 to 3 fold) in many different studies in A. annua ( Han et al, 2006 ; Aquil et al, 2009 ; Banyai et al, 2010a ; Nafis et al, 2011 ; Xiang et al, 2012 ; Ma et al, 2017a ). Co-expression of FPS, CYP71AV1 and its redox partner, POR (cytochrome P450 reductase) increased production by 3.6 fold, whereas combining four genes ADS, CYP71AV1, ALDH1, and POR from A. annua yielded a 3.4 fold increase in the artemisinin levels ( Chen et al, 2013 ; Shi et al, 2017 ). Additionally, the production also increased by overexpression of ADS, CYP71AV1, and HMGR ( Ma et al, 2009 ; Alam et al, 2016 ).…”

Section: Bioengineering Of Artemisinin Production In Green Plant Cellmentioning

confidence: 99%

A Review of Biotechnological Artemisinin Production in Plants

2017

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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.

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The stacked over-expression of FPS, CYP71AV1 and CPR genes leads to the increase of artemisinin level in Artemisia annua L.

Cited by 31 publications

References 35 publications

The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants

The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants

AaABCG40 Enhances Artemisinin Content and Modulates Drought Tolerance in Artemisia annua

A Review of Biotechnological Artemisinin Production in Plants

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