{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:31:40Z","timestamp":1791664300250,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFD2401904"],"award-info":[{"award-number":["2024YFD2401904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2024-MSLH-055"],"award-info":[{"award-number":["2024-MSLH-055"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cooking liquid from Manila clam (Ruditapes philippinarum) is an underutilized byproduct rich in water-soluble taste compounds, representing a potential source of natural umami peptides. In this study, peptide fractions were separated from the cooking liquid. A total of 764 peptide sequences were identified from the most potent fraction, F3 (&lt;3 kDa), by UPLC-ESI-Q-TOF-MS\/MS. Machine learning prediction and molecular docking were further used for screening. Five candidate peptides were selected: TQDTVVALDA, KEY, YKD, RND, and GEAF. Sensory evaluation (on a 0\u20135 scale) and electronic tongue measurements independently confirmed that peptide YKD possessed the strongest taste profile, with an electronic tongue relative umami score of 8.81 \u00b1 0.22. Furthermore, cell-based assays demonstrated that YKD effectively up-regulated the transcriptional expression of taste-related receptors, including GPRC6A, in STC-1 cells, revealing a multi-receptor synergetic mechanism for umami perception. In STC-1 cells, all peptides induced intracellular Ca2+ responses and showed no obvious cytotoxicity at 0.5\u20138.0 mmol\/L. YKD produced the highest fluorescence response (0.59) at 1.0 mmol\/L. Quantitative RT-PCR analysis suggested that YKD was associated with T1R1\/T1R3-related expression, whereas TQDTVVALDA induced stronger CaSR expression. These findings elucidate the specific peptide sequence that engages multiple receptors to create complex tastes, providing a theoretical basis for converting seafood processing byproducts into natural flavor enhancers.<\/jats:p>","DOI":"10.3390\/molecules31122193","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T08:19:52Z","timestamp":1782202792000},"page":"2193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery and Putative Perception Mechanisms of Novel Umami Peptides from Ruditapes philippinarum Cooking Liquid: In Silico Screening, Molecular Docking, Sensory Evaluation, and STC-1 Cell-Based Validation"],"prefix":"10.3390","volume":"31","author":[{"given":"Ruiying","family":"Wang","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Dalian Ocean University, Dalian 116023, China"},{"name":"Dalian Key Laboratory of Marine Bioactive Substances Development and High Value Utilization, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Dalian Ocean University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Dalian Ocean University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Dalian Ocean University, Dalian 116023, China"},{"name":"Dalian Key Laboratory of Marine Bioactive Substances Development and High Value Utilization, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanye","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Dalian Ocean University, Dalian 116023, China"},{"name":"Dalian Key Laboratory of Marine Bioactive Substances Development and High Value Utilization, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiancheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Dalian Ocean University, Dalian 116023, China"},{"name":"Dalian Key Laboratory of Marine Bioactive Substances Development and High Value Utilization, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibo","family":"Li","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Dalian Ocean University, Dalian 116023, China"},{"name":"Dalian Key Laboratory of Marine Bioactive Substances Development and High Value Utilization, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147501","DOI":"10.1016\/j.foodchem.2025.147501","article-title":"Exploring of novel salt-enhancing peptides from manila clam: Isolation, peptidomics and molecular characteristics","volume":"500","author":"Sun","year":"2026","journal-title":"Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145079","DOI":"10.1016\/j.foodchem.2025.145079","article-title":"Identification and molecular mechanisms of novel antioxidant peptides from Manila clam hydrolysate: Caenorhabditis elegans model, molecular simulations, and quantum chemistry","volume":"490","author":"Jia","year":"2025","journal-title":"Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, L., Fu, Z., Liu, Y., Song, Z., Yang, X., Yu, D., Wang, Q., Chi, H., and Zheng, J. 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