biostudies-literatureKnosp SMEXT | Japan Society for the Promotion of ScienceDeutsche Forschungsgemeinschaft (DFG)Agence Nationale de la Recherche (ANR)Uni Freiburg | Freiburg Institute for Advanced Studies, Albert-Ludwigs-Universität FreiburgUni Freiburg | Freiburg Institute for Advanced Studies, Albert-Ludwigs-Universität Freiburg (FRIAS)MEXT | Japan Society for the Promotion of Science (JSPS)Agence Nationale de la RechercheDeutsche ForschungsgemeinschaftConseil régional du Grand Est (Conseil Régional Grand Est)Ministère de l'Education Nationale, de l'Enseignement Superieur et de la RechercheConseil régional du Grand Est4092-4109https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405693biostudies-literatureUnknown43(18)The phenylpropanoid pathway is one of the plant metabolic pathways most prominently linked to the transition to terrestrial life, but its evolution and early functions remain elusive. Here, we show that activity of the t-cinnamic acid 4-hydroxylase (C4H), the first plant-specific step in the pathway, emerged concomitantly with the CYP73 gene family in a common ancestor of embryophytes. Through structural studies, we identify conserved CYP73 residues, including a crucial arginine, that have supported C4H activity since the early stages of its evolution. We further demonstrate that impairing C4H function via CYP73 gene inactivation or inhibitor treatment in three bryophyte species-the moss Physcomitrium patens, the liverwort Marchantia polymorpha and the hornwort Anthoceros agrestis-consisteThe EMBO journalAn ancient role for CYP73 monooxygenases in phenylpropanoid biosynthesis and embryophyte development.PMC11405693ANR-19-CE20-0017METABEVOOverseas Research FellowshipsANR-10-IDEX-0002-02VitestEXC-2189,CIBSSErhardt MWiedemann GKohchi TKnosp SMalherbe LRenault HKriegshauser LBakan BTatsumi KReski RfalseAn ancient role for CYP73 monooxygenases in phenylpropanoid biosynthesis and embryophyte development.The phenylpropanoid pathway is one of the plant metabolic pathways most prominently linked to the transition to terrestrial life, but its evolution and early functions remain elusive. Here, we show that activity of the t-cinnamic acid 4-hydroxylase (C4H), the first plant-specific step in the pathway, emerged concomitantly with the CYP73 gene family in a common ancestor of embryophytes. Through structural studies, we identify conserved CYP73 residues, including a crucial arginine, that have supported C4H activity since the early stages of its evolution. We further demonstrate that impairing C4H function via CYP73 gene inactivation or inhibitor treatment in three bryophyte species-the moss Physcomitrium patens, the liverwort Marchantia polymorpha and the hornwort Anthoceros agrestis-consiste2024-01-01T00:00:00Z2024 Sep2026-06-01T13:47:36.766Z2025-04-04T12:54:00.999ZS-EPMC114056933909043810.1038/s44318-024-00181-7