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When water-soluble sweet-tasting molecules enter the mouth, they dissolve in saliva and bind to sweet taste receptors on the surface of taste bud cells. The activation of these receptors by specific ligands results in the transduction of the chemical signal into a neural response, a process that is mediated by downstream signaling pathways. The primary sweet taste receptor, TAS1R2/TAS1R3, is a G protein-coupled receptor that requires the taste-specific G protein gustducin for sweet taste signal transduction. Binding of the ligand causes the gustducin heterotrimer to dissociate, with two major downstream signaling cascades that have been identified in humans. These are the α-gustducin-dependent signaling pathway for natural sweeteners, and the phospholipase Cβ2-dependent pathway for artificial sweeteners.
Natural sweeteners activate the α-gustducin pathway and induce the activation of adenylate cyclase, increasing the intracellular level of cAMP and leading to the activation of protein kinase A and inhibition of basolateral potassium channels, which eventually leads to an intracellular calcium ion influx and neurotransmitter release. Artificial sweeteners on the other hand are able to activate the PLCβ2 pathway, which hydrolyzes endogenous phospholipids, releasing calcium ions and activating TRPM5 channels, which in turn leads to ATP release and cell depolarization. The signals are then relayed to the brain by gustatory nerve fibers. Calcium ions, a key signaling molecule in the above-mentioned process are kept at a very low concentration by the highly efficient calcium pump and play a major role in the release of neurotransmitters.
Fig. 1 Schematic diagram of sweet taste signal transduction pathway. (Zhao X, et al. 2025)
References
The global prevalence of diabetes and obesity has led to an increased demand for low-sugar, nutrient-dense, and palatable foods. Chen J et al reported the development of an endogenous and “rapid validation–stable production” platform to produce foods with enhanced flavor, which was demonstrated in the edible tomato fruit. The authors combined two technologies in the MicroTom cherry tomato: TRV viral vector-mediated transient expression and Agrobacterium-mediated stable genetic transformation. The human sweet taste receptor TAS1R2 was used for in vitro functional validation and to unambiguously demonstrate that tomato-derived recombinant thaumatin II had receptor-binding activity equivalent to that of the native protein, rather than relying on conventional sensory-based evaluation methods. In addition, non-targeted metabolomic analysis showed that thaumatin II expression did not significantly affect the sugar, organic acid, or other major flavor compound profiles in tomato fruits, thereby providing safety information for “ready-to-eat sugar-substitute fruits.”
Fig. 2 Establishment and validation of the method for transient transfection of tomato plants with viruses. (Chen J, et al. 2025)
References
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