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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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Autores principales: Shen, Qian, Huang, Huayi, Xie, Lihui, Hao, Xiaolong, Kayani, Sadaf-Ilyas, Liu, Hang, Qin, Wei, Chen, Tiantian, Pan, Qifang, Liu, Pin, Tang, Kexuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207477/
https://www.ncbi.nlm.nih.gov/pubmed/35734250
http://dx.doi.org/10.3389/fpls.2022.885622
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author Shen, Qian
Huang, Huayi
Xie, Lihui
Hao, Xiaolong
Kayani, Sadaf-Ilyas
Liu, Hang
Qin, Wei
Chen, Tiantian
Pan, Qifang
Liu, Pin
Tang, Kexuan
author_facet Shen, Qian
Huang, Huayi
Xie, Lihui
Hao, Xiaolong
Kayani, Sadaf-Ilyas
Liu, Hang
Qin, Wei
Chen, Tiantian
Pan, Qifang
Liu, Pin
Tang, Kexuan
author_sort Shen, Qian
collection PubMed
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.
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spelling pubmed-92074772022-06-21 Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis Shen, Qian Huang, Huayi Xie, Lihui Hao, Xiaolong Kayani, Sadaf-Ilyas Liu, Hang Qin, Wei Chen, Tiantian Pan, Qifang Liu, Pin Tang, Kexuan Front Plant Sci Plant Science 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. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9207477/ /pubmed/35734250 http://dx.doi.org/10.3389/fpls.2022.885622 Text en Copyright © 2022 Shen, Huang, Xie, Hao, Kayani, Liu, Qin, Chen, Pan, Liu and Tang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Plant Science
Shen, Qian
Huang, Huayi
Xie, Lihui
Hao, Xiaolong
Kayani, Sadaf-Ilyas
Liu, Hang
Qin, Wei
Chen, Tiantian
Pan, Qifang
Liu, Pin
Tang, Kexuan
Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis
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 Plant Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207477/
https://www.ncbi.nlm.nih.gov/pubmed/35734250
http://dx.doi.org/10.3389/fpls.2022.885622
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