Enzymatic production of oroxylin A and hispidulin using a liverwort flavone 6-O-methyltransferase

Abstract

Oroxylin A and hispidulin, compounds which are abundant in both Scutellaria and liverwort species, are important lead compounds for the treatment of ischemic cerebrovascular disease. Their enzymatic synthesis requires an O-methyltransferase able to interact with the related flavonoid's 6-OH group, but such an enzyme has yet to be identified in plants. Here, the gene encoding an O-methyltransferase (designated PaF6OMT) was isolated from the liverwort species Plagiochasma appendiculatum. A test of alternative substrates revealed that its strongest preferences were baicalein and scutellarein, which were converted into, respectively, oroxylin A and hispidulin. Allowed a sufficient reaction time, the conversion rate of these two substrates was, respectively, 90% and 100%. PaF6OMT offers an enzymatic route to the synthesis of oroxylin A and hispidulin.

Keywords: O-methyltransferase; Plagiochasma appendiculatum; baicalein; liverworts; scutellarein.