Transcriptome analyses revealed the ultraviolet B irradiation and phytohormone gibberellins coordinately promoted the accumulation of artemisinin in Artemisia annua L.

Xiaofeng Shen,Tianyuan Zhang,Han Gao,Tingyu Ma,Dong Zhang,Li Xiang,Shilin Chen,Yuhua Shi,Lan Wu

doi:10.1186/s13020-020-00344-8

Abstract

BackgroundArtemisinin-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.MethodsArtemisinin 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.ResultsIn 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.ConclusionOur 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.

Highlights

Artemisinin-based combination therapy has become the preferred approach for treating malaria and has successfully reduced malaria-related mortality
Artemisinin concentrations in plants subjected to the GA + UV treatment were found to be notably higher than those in plants exposed to Ultraviolet B irradiation (UV-B) only (Fig. 1)
Identification of co‐expressed transcription factors and artemisinin biosynthesis genes Among the differentially expressed genes (DEGs) detected, we identified a total of 1295 transcription factors (TFs), which were subjected to co-expression analysis to identify those TFs involved in the regulation of genes associated with artemisinin biosynthesis

Summary

Introduction

Artemisinin-based combination therapy has become the preferred approach for treating malaria and has successfully reduced malaria-related mortality. The main source of artemisinin is Artemisia annua L., and it is of strategic importance to enhance artemisinin contents in A. annua plants. We performed transcriptome and metabolome analyses revealed that ultraviolet B irradiation and phytohormone gibberellins coordinately promoted the accumulation of artemisinin in Artemisia annua. Artemisinin is used as a first line and effective drug for the treatment of malaria, which is caused by the Plasmodium falciparum parasite [1]. The WHO recommended the use of artemisinin-based combination therapies (ACTs), which is the most effective malaria treatment available at present [2]. The sesquiterpene artemisinin derived from the medicinal plant Artemisia annua, which is remain the main and only natural source of artemisinin. Enhancing the content of artemisinin in A. annua plants would be highly desirable

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