Two types of O-methyltransferase are involved in biosynthesis of anticancer methoxylated 4'-deoxyflavones in Scutellaria baicalensis Georgi.
Meng-Ying CuiAn-Rui LuJian-Xu LiJie LiuYu-Min FangTian-Lin PeiXin ZhongYu-Kun WeiYu KongWen-Qing QiuYong-Hong HuJun YangXiao-Ya ChenCathie MartinQing ZhaoPublished in: Plant biotechnology journal (2021)
The medicinal plant Scutellaria baicalensis Georgi is rich in specialized 4'-deoxyflavones, which are reported to have many health-promoting properties. We assayed Scutellaria flavones with different methoxyl groups on human cancer cell lines and found that polymethoxylated 4'-deoxyflavones, like skullcapflavone I and tenaxin I have stronger ability to induce apoptosis compared to unmethylated baicalein, showing that methoxylation enhances bioactivity as well as the physical properties of specialized flavones, while having no side-effects on healthy cells. We investigated the formation of methoxylated flavones and found that two O-methyltransferase (OMT) families are active in the roots of S. baicalensis. The Type II OMTs, SbPFOMT2 and SbPFOMT5, decorate one of two adjacent hydroxyl groups on flavones and are responsible for methylation on the C6, 8 and 3'-hydroxyl positions, to form oroxylin A, tenaxin II and chrysoeriol respectively. The Type I OMTs, SbFOMT3, SbFOMT5 and SbFOMT6 account mainly for C7-methoxylation of flavones, but SbFOMT5 can also methylate baicalein on its C5 and C6-hydroxyl positions. The dimethoxylated flavone, skullcapflavone I (found naturally in roots of S. baicalensis) can be produced in yeast by co-expressing SbPFOMT5 plus SbFOMT6 when the appropriately hydroxylated 4'-deoxyflavone substrates are supplied in the medium. Co-expression of SbPFOMT5 plus SbFOMT5 in yeast produced tenaxin I, also found in Scutellaria roots. This work showed that both type I and type II OMT enzymes are involved in biosynthesis of methoxylated flavones in S. baicalensis.
Keyphrases
- cell wall
- cell cycle arrest
- mental health
- healthcare
- palliative care
- endothelial cells
- public health
- poor prognosis
- oxidative stress
- physical activity
- cell death
- papillary thyroid
- dna methylation
- saccharomyces cerevisiae
- signaling pathway
- genome wide
- cell proliferation
- mass spectrometry
- long non coding rna
- induced pluripotent stem cells
- health promotion
- drug discovery