Intrinsic Sweetness and Sweetness-Enhancing Property of β-Damascone

β-Damascone is a naturally occurring aroma compound with pronounced fruity-floral and “sweet-smelling” notes. Although well characterized olfactorily, its gustatory role and sweetness-enhancing property remain poorly understood. Here, we investigated the intrinsic sweetness of β-damascone and its ability to enhance sucrose-induced sweetness using an integrative approach combining sensory evaluation, electroencephalography (EEG), molecular docking, and molecular dynamics simulations. Sensory evaluation showed that β-damascone alone elicited negligible sweetness, but significantly amplified and prolonged sucrose-induced sweetness. EEG measurements further revealed strengthened cortical responses during co-stimulation with sucrose. Using a cryo-EM–derived full-length TAS1R2–TAS1R3-membrane model, molecular simulations demonstrated that β-damascone binds to a peripheral region of LB1–LB2 cleft in TAS1R2 VFD, stabilizing its closed conformation. β-Damascone also facilitated conformational rearrangements associated with receptor activation, including widening of the intracellular G-protein-binding cavity. Collectively, these findings provide mechanistic evidence that β-damascone acts as a synergistic enhancer of sucrose sweetness, supporting its potential for sugar-reduction applications.