Biosensor for bitterness-based plant compounds detection using human bitter taste receptor-derived peptide

To deal with environmental pressures and natural enemies, organisms generate a variety of natural products with pharmacological activities. Due to their chemical defense mechanisms, these natural products often have a bitter taste. Cnicin is a bitter sesquiterpene lactone derived from plants, which possesses multiple pharmacological properties such as antibacterial and anti-cancer activities. There were limitations in the detection research of cnicin before, and there is an urgent need for innovative detection strategies. In this study, the molecular docking technique was employed to identify the binding sites of a human taste receptor TAS2R46 for recognizing cnicin. And a taste receptor-derived peptide biosensor (TRP-sensor) for detecting cnicin was fabricated. This biosensor was capable of detecting cnicin at a concentration as low as 1 fM, which is one order of magnitude lower than the lowest detection limit reported so far. The sensor could detect cnicin in real time with high sensitivity and selectivity. Meanwhile, it also showed excellent performance in terms of operation and storage stability, and could accurately detect cnicin in the samples of Centaurea benedicta, a plant rich in cnicin. Therefore, the TRP sensor could be applied to screen for cnicin in natural products and could also be utilized in the food and pharmaceutical industries.