Parallel evolution of UbiA superfamily proteins into aromaticO-prenyltransferases in plants

Plants produce approximately 300 aromatic molecules enzymatically linked to prenyl side chains via C-O bonds. These O -prenylated aromatics have been found in taxonomically distant plant taxa as compounds beneficial or detrimental to human health, with O -prenyl moieties often playing crucial roles in their biological activities. To date, however, no plant gene encoding an aromatic O -prenyltransferase ( O -PT) has been described. This study describes the isolation of an aromatic O -PT gene, CpPT1 , belonging to the UbiA superfamily, from grapefruit ( Citrus × paradisi, Rutaceae). This gene is responsible for the biosynthesis of O -prenylated coumarin derivatives that alter drug pharmacokinetics in the human body. Another coumarin O -PT gene of the same protein family was identified in Angelica keiskei , an apiaceous medicinal plant containing pharmaceutically active O -prenylated coumarins. Phylogenetic analysis of these O -PTs suggested that aromatic O -prenylation activity evolved independently from the same ancestral gene in these distant plant taxa. These findings shed light on understanding the evolution of plant secondary metabolites via the UbiA superfamily.