Scientists Elucidate the Whole Biosynthesis Pathway of Baicalein in Scutellaria Baicalensis

Scutellaria baicalensis Georgi, or Huangqin, is a species of flowering plant in the Lamiaceae family. This medicinal plant has been widely used in China for thousands of years. Flavones like baicalein and wogonin are the major bioactive compounds extracted from the root of S. baicalensis. In previous studies, these flavones have demonstrated various pharmacological functions, such as hepatoprotection, antibacterial and antiviral, antioxidant, anticonvulsant and neuroprotective effects. Furthermore, apoptosis, induced from these compounds, can be used in stemming cancer cells without effects on normal cells.

Recently, scientists at Chenshan Botanical Garden/Shanghai Chenshan Plant Science Research Center of Chinese Academy of Sciences and John Innes Centre of UK, led by Prof. Cathie Martin and Dr. ZHAO Qing have successfully elucidated the whole biosynthesis pathway of baicalein in Scutellaria baicalensis.

Their research reported the identification of two flavone hydroxylases from S. baicalensis; they all belong to plant Cyt p450 enzymes and have higher expression levels in roots of Scutellaria. Of the two, one is called SbCYP82D1.1. Yeast enzyme assay experiment showed that SbCYP82D1.1 is a flavone 6-hydroxylase, which could convert chrysin and apigenin to produce baicalein and scutellarein, respectively. When the transcripts of SbCYP82D1.1 were down-regulated using RNAi, baicalein content level decreased tremendously while chrysin glycosides would heap up in the RNAi hairy roots.

SbCYP82D2, another enzyme, likely evolved from SbCYP82D1.1 through gene duplication. Interestingly, the protein encoded by SbCYP82D2 is a flavone 8-hydroxylase, and only permits chrysin as substrate in norwogonin production. Further study showed that when SbCYP82D1.1 and SbCYP82D2 were over-expressed in Arabidopsis and feed on the transgenic plants with chrysin, baicalin and norwogonin can be detected in these plants, indicating the enzymes worked in planta.

This discovery extends our previous work to elucidate the entire biosynthetic pathway for baicalein. It would lay a solid foundation for enhancing production of the specific flavones in Scutellaria plants or, alternatively, synthesizing them in novel hosts.

The paper, entitled “Two CYP82D enzymes function as flavone hydroxylases in the biosynthesis of root-specific 4′-deoxyflavones in Scutellaria baicelensis”, has been published online in Molecular Plant on 22th August, 2017. It was supported by Chenshan Special Fund for Shanghai Landscaping Administration Bureau Program and Natural Science Foundation of China.

Article website: http://www.cell.com/molecular-plant/abstract/S1674-2052(17)30239-3
 

Top-left: Scutellaria baicelensis plant
Top-middle: Dried root in traditional medicine
Bottom-left: Major flavone structures  in Scutellaria
Left: Pathway for beicalein

Author contact:
Dr. Cathie Martin, Professor
Chenshan Botanical Garden
Shanghai Chenshan Plant Science Research Center
Chinese Academy of Sciences
Chen Hua Road, Songjiang District
Shanghai 201602
Tel: +44 (0) 1603 450275
E-mail: cathie.martin@jic.ac.uk