Parallel evolution of UbiA superfamily proteins into aromatic O -prenyltransferases in plants

Significance Plants produce approximately 300 O -prenylated aromatics, with their O -prenyl moieties often being crucial to their bioactivities. This study identified a gene from grapefruit encoding an aromatic O -prenyltransferase ( O- PT) belonging to the UbiA superfamily. The O -PT was shown responsible for the biosynthesis of pharmaceutically active O -prenylated coumarins that cause grapefruit–drug interactions, an adverse effect disturbing the pharmacokinetics of more than 85 medications. Another UbiA O -PT for coumarins was isolated from Angelica keiskei , an apiaceous medicinal plant. Phylogenetic analysis of the rutaceous and apiaceous O -PTs suggested that aromatic O -prenylation activity emerged in parallel in these distant plant taxa. The molecular evolution of aromatic O -PTs from plant UbiA proteins may aid citrus breeding and a synthetic biology approach to bioactive O -prenylated coumarins.