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.

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两种O-甲基转移酶参与黄芩抗癌甲氧基化4'-脱氧黄酮的生物合成

药用植物黄芩黄芩富含特殊的 4'-脱氧黄酮，据报道其具有许多促进健康的特性。我们对人类癌细胞系中具有不同甲氧基的黄芩黄酮进行了检测，发现多甲氧基化的 4'-脱氧黄酮，如黄芩黄酮 I 和黄芩苷 I 与未甲基化的黄芩素相比，具有更强的诱导细胞凋亡的能力，表明甲氧基化可增强生物活性和物理特性专门的黄酮，同时对健康细胞没有副作用。我们研究了甲氧基化黄酮的形成，发现两个O-甲基转移酶 (OMT) 家族在黄芩的根中具有活性. II型OMT，SbPFOMT2和SbPFOMT5，修饰黄酮上两个相邻的羟基之一，负责C6、8和3'-羟基位置的甲基化，分别形成oroxylin A、tenaxin II和chrysoeriol。I 型 OMT、SbFOMT3、SbFOMT5 和 SbFOMT6 主要负责黄酮的 C7-甲氧基化，但 SbFOMT5 还可以甲基化黄芩素的 C5 和 C6-羟基位置。二甲氧基黄酮，黄芩黄酮 I（天然存在于黄芩的根中）) 可以通过在培养基中提供适当羟基化的 4'-脱氧黄酮底物时共表达 SbPFOMT5 和 SbFOMT6 在酵母中产生。SbPFOMT5 和 SbFOMT5 在酵母中的共表达产生了tenaxin I，也存在于黄芩根中。本研究表明，I型和II型OMT酶都参与了黄芩甲氧基黄酮的生物合成。