Metabolic engineering to enhance the accumulation of bioactive flavonoids licochalcone A and echinatin in Glycyrrhiza inflata (Licorice) hairy roots

作者：Zhigeng Wu, Sanjay K. Singh, Ruiqing Lyu, Sitakanta Pattanaik, Ying Wang, Yongqing Li, Ling Yuan, Yongliang Liu · 发表于：Frontiers in Plant Science · 年份：2022 · DOI：10.3389/fpls.2022.932594 · 被引用次数：30 · 研究领域：Pharmacological Effects of Natural Compounds、Ginseng Biological Effects and Applications、Genomics, phytochemicals, and oxidative stress

Echinatin and licochalcone A (LCA) are valuable chalcones preferentially accumulated in roots and rhizomes of licorice ( Glycyrrhiza inflata ). The licorice chalcones (licochalcones) are valued for their anti-inflammatory, antimicrobial, and antioxidant properties and have been widely used in cosmetic, pharmaceutical, and food industries. However, echinatin and LCA are accumulated in low quantities, and the biosynthesis and regulation of licochalcones have not been fully elucidated. In this study, we explored the potential of a R2R3-MYB transcription factor (TF) AtMYB12 , a known regulator of flavonoid biosynthesis in Arabidopsis , for metabolic engineering of the bioactive flavonoids in G. inflata hairy roots. Overexpression of AtMYB12 in the hairy roots greatly enhanced the production of total flavonoids (threefold), echinatin (twofold), and LCA (fivefold). RNA-seq analysis of AtMYB12 -overexpressing hairy roots revealed that expression of phenylpropanoid/flavonoid pathway genes, such as phenylalanine ammonia-lyase ( PAL ), chalcone synthase ( CHS ), and flavanone 3’-hydroxylase ( F3’H ), is significantly induced compared to the control. Transient promoter activity assay indicated that AtMYB12 activates the GiCHS1 promoter in plant cells, and mutation to the MYB-binding motif in the GiCHS1 promoter abolished activation. In addition, transcriptomic analysis revealed that AtMYB12 overexpression reprograms carbohydrate metabolism likely to increase carbon flux into flavonoid b...