A Novel Peptide Derived from Casein Hydrolysates as a Growth Factor for Lactobacillus delbrueckii subsp. bulgaricus sp1.1.

Milk proteins are traditionally recognized as nitrogen sources that support lactic acid bacteria (LAB) proliferation. Notably, oligopeptides may serve as the primary nitrogen source, and have the potential of enhancing the resistance of microbial strains to acidic environments. In this study, the impact of various casein hydrolysates on the proliferation of L. delbrueckii subsp. bulgaricus sp1.1 and the composition of peptides was studied. This study unveiled a novel peptide, KEGIHAQ, with a significant capacity to enhance both acid tolerance and proliferation of LAB. Inclusion of 0.1% (w/v) KEGIHAQ increased the number of viable bacteria by 1.68 times compared with the control and attained 1.34 × 10⁹ CFU/mL, and under acid stress, the number of viable bacteria was 1.41 times that of the control. Transcriptomic analysis revealed that KEGIHAQ was not directly assimilated by L. delbrueckii subsp. bulgaricus sp1.1; instead, it acted as an effector, which upregulated the dipeptide transporter protein DppA and amino acid metabolism genes. This facilitated dipeptide uptake, amino acid synthesis, energy generation, and various bacterial physiological activities, while enhancing bacterial acid resistance mechanisms. These results provided valuable insights in identifying target peptides for nitrogen sources in future LAB high-density cultures, whether through biosynthesis or chemical synthesis.