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

Fermentation is applied to improve bioactive components (e.g., 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.