Identification of Tyrosinase Inhibitory Peptides from Sea Cucumber (Apostichopus japonicus) Collagen by in silico Methods and Study of their Molecular Mechanism

Aims: Identify novel tyrosinase inhibitory peptides from sea cucumber (Apostichopus japonicus) collagen using in silico methods and elucidate the molecular interaction mechanism.Background: Tyrosinase is a key enzyme in the melanin biosynthesis pathway, to restrain melanin production and reduce the appearance of associated skin diseases, inhibition of tyrosinase activity is one of the most effective methods.Objectives: The collagen from Apostichopus japonicus, which consists of 3,700 amino acid residues, was obtained from the National Center for Biotechnology Information (NCBI) as the accession number of PIK45888.Methods: Virtual hydrolyzed method was used, and the peptides generated were compared to the previously established BIOPEP-UWM database. In addition, peptides were examined for their solubility, toxicity, and tyrosinase-binding capacity.Results: A tripeptide CME with optimal potential inhibitory activity against tyrosinase was identified, and its inhibitory activity was validated by in vitro experiments. The IC50 value of CME was 0.348 +/- 0.02 mM for monophenolase, which was inferior to the positive control peptide glutathione, while it had an IC50 value of 1.436 +/- 0.07 mM for diphenolase, which was significantly better than glutathione, and the inhibition effect of CME on tyrosinase was competitive and reversible.Conclusion: In silico methods were efficient and useful in the identification of new peptides.