Dataset Information

Red and Blue Light Promote the Accumulation of Artemisinin in Artemisia Annua L.

ABSTRACT: Artemisinin, which has been isolated from Artemisiaannua L., is the most effective antimalarial drug and has saved millions of lives. In addition, artemisinin and its derivatives have anti-tumor, anti-parasitic, anti-fibrosis, and anti-arrhythmic properties, which enhances the demand for these compounds. Improving the content of artemisinin in A.annua is therefore becoming an increasing research interest, as the chemical synthesis of this metabolite is not viable. Ultraviolet B and C irradiation have been reported to improve the artemisinin content in A.annua, but they are harmful to plant growth and development. Therefore, we screened other light sources to examine if they could promote artemisinin content without affecting plant growth and development. We found that red and blue light could enhance artemisinin accumulation by promoting the expression of the genes that were involved in artemisinin biosynthesis, such as amorpha-4,11-diene synthase (ADS) and cytochrome P450 monooxygenase (CYP71AV1) genes. Thus, in addition to being the main light sources for photosynthesis, red and blue light play a key role in plant secondary metabolism, and optimizing the combination of these light might allow for the productionof artemisinin-rich A.annua.

SUBMITTER: Zhang D

PROVIDER: S-EPMC6100300 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Red and Blue Light Promote the Accumulation of Artemisinin in Artemisia Annua L.

Zhang Dong D Sun Wei W Shi Yuhua Y Wu Lan L Zhang Tianyuan T Xiang Li L

Molecules (Basel, Switzerland) 20180531 6

Artemisinin, which has been isolated from Artemisiaannua L., is the most effective antimalarial drug and has saved millions of lives. In addition, artemisinin and its derivatives have anti-tumor, anti-parasitic, anti-fibrosis, and anti-arrhythmic properties, which enhances the demand for these compounds. Improving the content of artemisinin in A.annua is therefore becoming an increasing research interest, as the chemical synthesis of this metabolite is not viable. Ult ...[more]

PMID: 29857558

Similar Datasets

Project description:Despite of many advances in the treatment of malaria, it is still the fifth most prevalent disease worldwide and is one of the major causes of death in the developing countries which accounted for 584,000 deaths in 2013, as estimated by World Health Organization. Artemisinin from Artemisia annua is still one of the most effective treatments for malaria. Increasing the artemisinin content of A. annua plants by genetic engineering would improve the availability of this much-needed drug.In this regard, a high artemisinin-yielding hybrid of A. annua produced by the centre for novel agricultural products of the University of York, UK, was selected (artemisinin maximally 1.4 %). As rol genes are potential candidates of biochemical engineering, genetic transformation of A. annua with Agrobacterium tumefaciens GV3101 harbouring vectors with rol B and rol C genes was carried out with the objective of enhancement of artemisinin content. Transgenic lines produced were analysed by the LC-MS for quantitative analysis of artemisinin and analogues. These high artemisinin yielding transgenics were also analysed by real time quantitative PCR to find the molecular dynamics of artemisinin enhancement. Genes of artemisinin biosynthetic pathway were studied including amorphadiene synthase (ADS), cytochrome P450, (CYP71AV1) and aldehyde dehydrogenase 1 (ALDH1). Trichome-specific fatty acyl-CoA reductase 1(TAFR1) is an enzyme involved in both trichome development and sesquiterpenoid biosynthesis and both processes are important for artemisinin biosynthesis. Thus, real time qPCR analysis of the TAFR1 gene was carried out, and trichome density was determined.Transgenics of rol B gene showed two- to ninefold (the decimal adds nothing in the abstract, please simplify to two- to ninefold) increase in artemisinin, 4-12-fold increase in artesunate and 1.2-3-fold increase in dihydroartemisinin. Whereas in the case of rol C gene transformants, a fourfold increase in artemisinin, four to ninefold increase in artesunate and one- to twofold increase in dihydroartemisinin concentration was observed. Transformants with the rol B gene had higher expression of these genes than rol C transformants. TAFR1 was also found to be more expressed in rol gene transgenics than wild type A. annua, which was also in accordance with the trichome density of the respective plant.Thus it was proved that rol B and rol C genes are effective in the enhancement of artemisinin content of A. annua, rol B gene being more active to play part in this enhancement than rol C gene.

Project description:Artemisinin is a sesquiterpene lactone endoperoxide extracted from a traditional Chinese medicinal plant Artemisia annua. Artemisinin-based combination therapies (ACTs) are recommended as the best treatment of malaria by the World Health Organization (WHO). Both the phytohormone jasmonic acid (JA) and light promote artemisinin biosynthesis in A. annua. Interestingly, we found that the increase of artemisinin biosynthesis by JA was dependent on light. However, the relationship between the two signal pathways mediated by JA and light remains unclear. Here, we collected the A. annua seedlings of 24 h continuous light (Light), 24 h dark treatment (Dark), 4 h MeJA treatment under the continuous light conditions (Light-MeJA-4h) and 4 h MeJA treatment under the dark conditions (Dark-MeJA-4h) and performed the transcriptome sequencing using Illumina HiSeq 4000 System. A total of 266.7 million clean data were produced and assembled into 185,653 unigenes, with an average length of 537 bp. Among them, 59,490 unigenes were annotated and classified based on the public information. Differential expression analyses were performed between Light and Dark, Light and Light-MeJA-4h, Dark and Dark-MeJA-4h, Light-MeJA-4h, and Dark-MeJA-4h, respectively. Furthermore, transcription factor (TF) analysis revealed that 1588 TFs were identified and divided into 55 TF families, with 284 TFs down-regulated in the Dark relative to Light and 96 TFs up-regulated in the Light-MeJA-4h relative to Light. 8 TFs were selected as candidates for regulating the artemisinin biosynthesis and one of them was validated to be involved in artemisinin transcriptional regulation by Dual-Luciferase (Dual-LUC) assay. The transcriptome data shown in our study offered a comprehensive transcriptional expression pattern influenced by the MeJA and light in A. annua seedling, which will serve as a valuable resource for further studies on transcriptional regulation mechanisms underlying artemisinin biosynthesis.

Project description:Background:Artemisinin-based combination therapy has become the preferred approach for treating malaria and has successfully reduced malaria-related mortality. Currently, the main source of artemisinin is Artemisia annua L., and thus, it is of strategic importance to enhance artemisinin contents in A. annua plants. Phytohormones and illumination are known to be important external environmental factor that can have notable effects on the production of secondary metabolite. The activities of different hormones can be influenced to varying degrees by light, and thus light and hormones may jointly regulate various processes in plants. Here, we performed transcriptome and metabolome analyses revealed that ultraviolet B irradiation and phytohormone gibberellins coordinately promoted the accumulation of artemisinin in Artemisia annua. Methods:Artemisinin analysis was performed by ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-ESI-QqQ-MS/MS). RNA sequencing, GO and KEGG enrichment analysis were applied to analyzing the differentially expressed genes (DEGs) under ultraviolet B irradiation and gibberellins treatments. Weighted gene co-expression network (WGCNA) analyzed the genes in artemisinin?related modules and identified candidate hub genes in these modules. Results:In this study, we found that cross-talk between UV-B and GA induced processes leading to modifications in artemisinin accumulation. A total of 14,762 genes differentially expressed (DEGs) among different treatments were identified by transcriptome analysis. UV-B and GA treatments enhanced the accumulation of artemisinin by up-regulating the expression of the key artemisinin biosynthesis genes ADS and CYP71AV1. According to the high degree value and high expression level, a total of 84 co-expressed transcription factors were identified. Among them, MYB and NAC TFs mainly involved in regulating the biosynthesis of artemisinin. Weighted gene co-expression network analysis revealed that GA?+?UV in blue modules was positively correlated with artemisinin synthesis, suggesting that the candidate hub genes in these modules should be up-regulated to enhance artemisinin synthesis in response to GA?+?UV treatment. Conclusion:Our study demonstrated the co-regulation of artemisinin biosynthetic pathway genes under ultraviolet B irradiation and phytohormone gibberellins treatment. The co-expression was analysis revealed that the selected MYB and NAC TFs might have regulated the artemisinin biosynthesis gene expression with ADS and CYP71AV1 genes. Weighted gene co-expression network analysis revealed that GA?+?UV treatment in blue modules was positively correlated with artemisinin synthesis. We established the network to distinguish candidate hub genes in blue modules might be up-regulated to enhance artemisinin synthesis in response to GA?+?UV treatment.

Project description:Commercial Artemisia annua crops are the sole source of artemisinin (ART) worldwide. Data on seasonal accumulation and peak of sesquiterpenes, especially ART in commercial A. annua, is lacking while current breeding programs focus only on ART and plant biomass, but ignores dihydroartemisinic acid (DHAA) and artemisinic acid (AA). Despite past breeding successes, plants richer in ART are needed to decrease prices of artemisinin-combination therapy (ACT). Our results show that sesquiterpene concentrations vary greatly along the growing season and that sesquiterpene profiles differ widely among chemotypes. Field studies with elite Brazilian, Chinese, and Swiss germplasms established that ART peaked in vegetative plants from late August to early September, suggesting that ART is related to the photoperiod, not flowering. DHAA peaks with ART in Chinese and Swiss plants, but decreases, as ART increases, in Brazilian plants, while AA remained stable through the season in these genotypes. Chinese plants peaked at 0.9% ART, 1.6% DHAA; Brazilian plants at 0.9% ART, with less than 0.4% DHAA; Swiss plants at 0.8% ART and 1% DHAA. At single-date harvests, seeded Swiss plants produced 0.55-1.2% ART, with plants being higher in DHAA than ART; Brazilian plants produced 0.33-1.5% ART, with most having higher ART than DHAA. Elite germplasms produced from 0.02-0.43% AA, except Sandeman-UK (0.4-1.1% AA). Our data suggest that different chemotypes, high in ART and DHAA, have complementary pathways, while competing with AA. Crossing plants high in ART and DHAA may generate hybrids with higher ART than currently available in commercial germplasms. Selecting for high ART and DHAA (and low AA) can be a valuable approach for future selection and breeding to produce plants more efficient in transforming DHAA into ART in planta and during post-harvest. This novel approach could change the breeding focus of A. annua and other pharmaceutical species that produce more than one desired metabolite in the same pathway. Obtaining natural variants with high ART content will empower countries and farmers who select, improve, and cultivate A. annua as a commercial pharmaceutical crop. This selection approach could enable ART to be produced locally where it is most needed to fight malaria and other parasitic neglected diseases.

Dataset Information

Red and Blue Light Promote the Accumulation of Artemisinin in Artemisia Annua L.

Publications

Red and Blue Light Promote the Accumulation of Artemisinin in Artemisia Annua L.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets