Soybean fermentation drives the production of native neuroprotective peptides based on a peptidomics strategy

Fermentation is applied to improve bioactive components (<i>e.g.</i>, native peptides and amino acids) responsible for health benefits. The native peptide identification is vital for precisely delineating fermented food properties. However, their identification represents a challenge due to large heterogeneity in sizes and charges. Herein, an LC-MS-based peptidomics approach was established to profile peptides in fermented soybean. As a result, a total of 714 native peptides, including 561 novel peptides were first detected and identified. Approximately 75 % of the peptides were unique or dramatically increased after fermentation. Interestingly, most peptides were released from two main soybean allergenic proteins, glycinin and β-conglycinin. Furthermore, molecular docking revealed the high binding affinity of newly identified peptides with monoamine oxidases (MAOs). The representative peptides, especially a peptide PLDLTSFVLHEAI hydrolyzed from toxic protein lectin, displayed good MAOs inhibitory effect with an IC₅₀ value of 0.073 ± 0.001 mM. Moreover, PLDLTSFVLHEAI and DVIS demonstrated neuroprotection in mouse neuroblastoma neuro 2A (N2A) cells. Overall, this study enriched the peptide diversity of fermented soybean and provided a scientific basis for bioactive peptides in fermented foods as functional ingredients. Moreover, this study provided a new insight into the development of functional foods that are beneficial for improving mental health.