Parallel evolution of UbiA superfamily proteins into aromatic <i>O</i> -prenyltransferases in plants
Ryosuke Munakata, Alexandre Olry, Tomoya Takemura, Kanade Tatsumi, Takuji Ichino, Cloé Villard, Joji Kageyama, Tetsuya Kurata, Masaru Nakayasu, Florence Jacob, Takao Koeduka, Hirobumi Yamamoto, Eiko Moriyoshi, Tetsuya Matsukawa, Jérémy Grosjean, Célia Krieger, Akifumi Sugiyama, Masaharu Mizutani, Frédéric Bourgaud, Alain Hehn, Kazufumi Yazaki
Abstract
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.