Identification, Characterization, and Catalytic Mechanism of Regioselective UbiA Prenyltransferases in Morus Plants

• DOI: 10.1002/ange.202504190
• Publication Date: 2025-03-13T16:14:56Z
• Authors: Shengzhi Liu; Yanxin Tao; Yuchao Zhang; Jiahui Gong; Zerong Wu; Zhao Wang; Zhoujie An; Runjie Shi; Yu Zhao; Eman Shawky; Zhichao Xu; Wei Zhu; Jingkui Tian
• Keywords: Identification

UbiA prenyltransferases (PTs) play an indispensable role in the prenylation of plant metabolites, yielding numerous natural products with enhanced pharmacological activities. These enzymes typically target specific carbon atoms or hydroxyl groups aromatic substrates. Despite recent identification dozens plant‐derived PTs, their catalytic mechanism remains poorly understood, particularly regarding precise control regioselectivity. Here we identified 10 MaPTs that catalyzed regioselective and geranylation moracin substrates Morus alba. Molecular dockings, dynamics simulations, quantum chemical calculations revealed substrate‐induced conformational changes leading to formation hydrophobic reaction pocket, as well differential binding between various M. Additionally, recognition prenyl donors by MaPT27 potential underlying reversal regioselectivity induced different were disscussed. Finally, structure‐based rational mutation altered site preference from C7 C5. findings suggest PTs is governed both inherent chemoselectivity sites intricate protein‐substrate interactions. results provide insights into facilitating application protein engineering synthetic biology for production prenylated compounds medicinal potential.