Parallel evolution of UbiA superfamily proteins into aromatic O-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.