A novel tyrosinase inhibitory peptide obtained from Sipunculus nudus gelatin hydrolysate: preparation, identification, and action mechanism

Tyrosinase inhibitory peptides (TIPs) derived from food resources have attracted immense attention in the food, cosmetic, and pharmaceutical industries owing to their excellent biological safety and ease of absorption. In this study, single-factor experiment and response surface optimization were used to prepare the Sipunculus nudus gelatin enzymatic hydrolysis (SNGH) product. Subsequently, a novel tyrosinase inhibitory peptide was screened out through ultrafiltration classification, biological activity prediction, molecular docking, and molecular dynamics simulation, and its inhibitory mechanism was analyzed. The results revealed that the optimal enzymatic hydrolysis process was: the enzyme addition was 4768.87 U/g, the enzymatic hydrolysis time was 4.72 h, and the enzymatic hydrolysis temperature was 42.76 °C. A total of 287 peptides were detected in the ultrafiltration component Ⅰ (SNGH-Ⅰ) with a high tyrosinase inhibitory activity, and 161 peptides with binding energies < -7.0 kcal/mol were screened out through molecular docking. Subsequently, 91 peptides with a biological activity score > 0.3 were obtained after biological activity screening. Finally, 5 possible TIPs were screened out according to their hydrophobicity, peptide score, and molecular weight. Among them, IIAPPERKY, VWDESFKVF, and FAGDDAPRAVFPS exhibited a superior tyrosinase inhibitory activity. Molecular dynamics simulations revealed that IIAPPERKY had better conformational stability and belonged to the group of reversible competitive inhibitors.