A cytosine analogue 5-azacitidine improves the accumulation of licochalcone A in licorice Glycyrrhiza inflata

• Published in: Journal of plant physiology 2024-01, Vol.292, p.154145-154145, Article 154145
• Main Authors: Ma, Xiaoling, Jiang, Ningxin, Fu, Jingxian, Li, Yuping, Zhou, Lijun, Yuan, Ling, Wang, Ying, Li, Yongqing
• Format: Article
• Language: English
• Subjects: 5-Azacitidine; antioxidants; Azacitidine; biosynthesis; bisulfites; Chalcones - pharmacology; Cytosine; DNA methylation; DNA methylation inhibitor; epigenetics; Flavonoid; flavonoids; gene expression regulation; genome; Glycyrrhiza - chemistry; Glycyrrhiza - genetics; Glycyrrhiza inflata; Licochalcone A; licorice; plant physiology; supply balance; transcriptomics
• ISSN: 0176-1617; 1618-1328
• DOI: 10.1016/j.jplph.2023.154145

Licochalcone A (LCA) is a characteristic compound of Glycyrrhiza inflata with anti-inflammatory, antioxidant and antitumor activities. However, G. inflata produces LCA in low quantities that does not meet the market demand. In this study, we found that DNA methylation inhibitor 5-azacitidine (5-azaC) successfully improved the LCA contents in G. inflata seedlings. Transcriptome analysis revealed a series of differentially expressed genes (DEGs), including transcription factors such as MYB, ERF, WRKY, and some structural genes related to flavonoid biosynthesis. However, whole genome bisulfite sequencing (BS-seq) results showed little effect of the 5-azaC treatment on the alteration of DNA methylation on these genes, indicating the possibility that 5-azaC acts as a stimulus, but not an epigenetic modulation factor to improve the LCA content in G. inflata. Additionally, we applied the 5-azaC treatment to field plants and hairy roots and successfully increased the LCA contents in both cases. This research demonstrates the feasibility of 5-azaC treatments in future applications to improve plant production of LCA. •The DNA methylation inhibitor 5-azacitidine (5-azaC) promotes licochalcone A (LCA) accumulation in Glycyrrhiza inflata seedlings.•5-azaC treatment activates a set of structural genes and transcription factors involved in the LCA biosynthesis and this process is independent on the alteration of DNA methylation level.•The 5-azaC is more likely acting as a stimulus, but not as an epigenetic modulation factor to improve the LCA content in G. inflata.•The 5-azaC treatment successfully improves LCA contents in field plants and hairy roots of G. inflata.