Elucidating odorant synergy in red wine: through olfactory receptor-based profiling

Abstract The flavor complexity of red wine stems from diverse aroma compounds and their interactions. Key odorants 2,3,5-trimethylpyrazine (TMP) and furfuryl alcohol (FA) contribute roasted/earthy and sweet/caramel-like notes, respectively, collectively shaping the wine’s sensory profile. However, the mechanism underlying their olfactory interaction remains unclear. In this study, human sensory evaluation revealed a mutual synergistic enhancement between TMP and FA. Cellular models expressing cognate receptors OR5K1 (TMP-specific) and OR2W1 (FA-responsive) were established, with intracellular cAMP detection confirming receptor-level synergy. Further molecular simulations predicted non-competitive binding mechanisms, as both odorants occupied distinct sites within their respective receptor pockets, consistent with observed non-antagonistic synergy. This work elucidates the molecular perceptual mechanism underlying key wine aroma interactions, providing a novel theoretical framework for understanding red wine flavor complexity.