Functional Characterization of an Aldol Condensation Synthase PheG for the Formation of Hispidin from Phellinus Igniarius

• DOI: 10.1002/advs.202413192
• Publication Date: 2025-01-28T18:09:16Z
• Authors: Wanting Zhang; Ruliang Zheng; Weiling Geng; Xinyuan Wu; Xiaojuan Gao; Li Zhou; Zhenyu An; Cheng Liu; Zhijun Song; Hongyan Ji; Hao Yang; Xiuli Wu
• Keywords: Aldol condensation; Aldol reaction; Condensation reaction

Abstract Hispidin ( 1 ) is a polyphenolic compound with wide range of pharmacological activities that distributed in both plants and fungi. In addition to natural extraction, hispidin can be obtained by chemical or enzymatic synthesis. this study, the identification characterization an undescribed enzyme, PheG, from Phellinus igniarius P. ), which catalyzes construction key C─C bond synthesis are reported. It demonstrated vitro PheG generates catalyzing formation aldol condensation reaction. Based on these results, plausible pathway for biosynthesis proposed utilizing primary triacetic acid lactone (TAL, 2 3,4‐dihydroxybenzaldehyde 3 ). The mechanisms reaction investigated using molecular dynamics (MD) simulations, mechanics/generalized Born surface area (MM/GBSA) binding free energy calculations, density functional theory, site‐specific mutations. locations amino residues catalyze conversion substrates at active site PheG‐1 identified. This study provides new method preparing high efficiency low cost.