PRJNA545532
Identification and characterization of novel flavonoid prenyltransferase and O-methyltransferase from the medicinal herb Epimedium
Prenylated flavonoids are plant specialized metabolites often found to possess unique bioactivities. The enzymes for the biosynthesis of the flavonoid core structure have been well characterized. However, many of the enzymes that add modifying chemical groups to the flavonoid core structure in plant specialized metabolism are still unknown. In particular, only a dozen plant flavonoid prenyltransferases have been characterized, and they are predominantly characterized from the Leguminosae family, restricting our understanding of how this class of enzymes functions more broadly. In this work, we identified and characterized two flavonoid-modifying enzymes from the medicinal plant Epimedium sagittatum. EsPTA is a flavonoid prenyltransferase, and EsOMTC is a flavonoid 4'-O-methyltransferase. EsPTA is the first flavonoid prenyltransferase described from the Berberidaceae family. Although the regiospecificity of the reaction catalyzed by EsPTA is still uncertain between C6- or C8-prenylation, this prenyltransferase is characterized by high substrate affinity compared to the majority of known plant flavonoid prenyltransferases. Furthermore, it is the first flavonoid prenyltransferase capable of prenylating a flavonol substrate. EsOMTC is a promiscuous enzyme, able to methylate a variety of functionalized flavonoids. As E. sagitattum produces several prenylated flavonoids with potent phosphodiesterase-5 inhibitory activity, the described characterization of E. sagitattum flavonoid-modifying enzymes will provide new tools for the biosynthetic production of these therapeutically promising prenylated flavonoids. The identification of a flavonoid prenyltransferase from this non-legume plant also provides additional insight into the evolution of this interesting class of enzymes.