Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis
Plants have evolved sophisticated systems for regulating the biosynthesis of specialized phytochemicals. Artemisinin, which is a sesquiterpene lactone widely used in anti-malaria treatment, is produced by the Artemisia annua L. plant. However, the artemisinin content in A. annua is low and difficult...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Plant Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpls.2022.885622/full |
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| author | Qian Shen Huayi Huang Lihui Xie Xiaolong Hao Xiaolong Hao Sadaf-Ilyas Kayani Hang Liu Wei Qin Tiantian Chen Qifang Pan Pin Liu Kexuan Tang |
| author_facet | Qian Shen Huayi Huang Lihui Xie Xiaolong Hao Xiaolong Hao Sadaf-Ilyas Kayani Hang Liu Wei Qin Tiantian Chen Qifang Pan Pin Liu Kexuan Tang |
| author_sort | Qian Shen |
| collection | DOAJ |
| description | Plants have evolved sophisticated systems for regulating the biosynthesis of specialized phytochemicals. Artemisinin, which is a sesquiterpene lactone widely used in anti-malaria treatment, is produced by the Artemisia annua L. plant. However, the artemisinin content in A. annua is low and difficult to meet market demands. Studies have shown that artemisinin biosynthesis in A. annua has complex temporal and spatial specificity and is under tightly transcriptional regulation. However, the mechanism of transcriptional regulation of artemisinin biosynthesis remains unclear. In this study, we identified two MYC-type bHLH transcription factors (AabHLH2 and AabHLH3) as novel regulators of artemisinin biosynthesis. These bHLH TFs act as transcription repressors and function redundantly to negatively regulate artemisinin biosynthesis. Furthermore, AabHLH2 and AabHLH3 are nuclear proteins that bind to DNA elements with similar specificity to that of AaMYC2, but lack the conserved activation domain, suggesting that repression is achieved by competition for the same cis-regulatory elements. Together, our findings reveal a novel artemisinin biosynthesis regulatory network, provide new insight into how specialized metabolites are modulated in plants, and propose a model in which different bHLH TFs coordinated in regulating artemisinin production in the plant. Finally, this study provides some useful target genes for metabolic engineering of artemisinin production via CRISPR/Cas9 gene editing. |
| first_indexed | 2024-12-11T18:24:51Z |
| format | Article |
| id | doaj.art-2bc103e68198477eb7191c87c6da58b4 |
| institution | Directory Open Access Journal |
| issn | 1664-462X |
| language | English |
| last_indexed | 2024-12-11T18:24:51Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Plant Science |
| spelling | doaj.art-2bc103e68198477eb7191c87c6da58b42022-12-22T00:55:07ZengFrontiers Media S.A.Frontiers in Plant Science1664-462X2022-06-011310.3389/fpls.2022.885622885622Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin BiosynthesisQian Shen0Huayi Huang1Lihui Xie2Xiaolong Hao3Xiaolong Hao4Sadaf-Ilyas Kayani5Hang Liu6Wei Qin7Tiantian Chen8Qifang Pan9Pin Liu10Kexuan Tang11Plant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlant Biotechnology Research Center, SJTU–Fudan–Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaPlants have evolved sophisticated systems for regulating the biosynthesis of specialized phytochemicals. Artemisinin, which is a sesquiterpene lactone widely used in anti-malaria treatment, is produced by the Artemisia annua L. plant. However, the artemisinin content in A. annua is low and difficult to meet market demands. Studies have shown that artemisinin biosynthesis in A. annua has complex temporal and spatial specificity and is under tightly transcriptional regulation. However, the mechanism of transcriptional regulation of artemisinin biosynthesis remains unclear. In this study, we identified two MYC-type bHLH transcription factors (AabHLH2 and AabHLH3) as novel regulators of artemisinin biosynthesis. These bHLH TFs act as transcription repressors and function redundantly to negatively regulate artemisinin biosynthesis. Furthermore, AabHLH2 and AabHLH3 are nuclear proteins that bind to DNA elements with similar specificity to that of AaMYC2, but lack the conserved activation domain, suggesting that repression is achieved by competition for the same cis-regulatory elements. Together, our findings reveal a novel artemisinin biosynthesis regulatory network, provide new insight into how specialized metabolites are modulated in plants, and propose a model in which different bHLH TFs coordinated in regulating artemisinin production in the plant. Finally, this study provides some useful target genes for metabolic engineering of artemisinin production via CRISPR/Cas9 gene editing.https://www.frontiersin.org/articles/10.3389/fpls.2022.885622/fullbHLHMYC2transcription regulationArtemisia annuaartemisinin |
| spellingShingle | Qian Shen Huayi Huang Lihui Xie Xiaolong Hao Xiaolong Hao Sadaf-Ilyas Kayani Hang Liu Wei Qin Tiantian Chen Qifang Pan Pin Liu Kexuan Tang Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis Frontiers in Plant Science bHLH MYC2 transcription regulation Artemisia annua artemisinin |
| title | Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis |
| title_full | Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis |
| title_fullStr | Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis |
| title_full_unstemmed | Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis |
| title_short | Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis |
| title_sort | basic helix loop helix transcription factors aabhlh2 and aabhlh3 function antagonistically with aamyc2 and are negative regulators in artemisinin biosynthesis |
| topic | bHLH MYC2 transcription regulation Artemisia annua artemisinin |
| url | https://www.frontiersin.org/articles/10.3389/fpls.2022.885622/full |
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