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

  • Appl Biochem Biotechnol. 2025 Sep;197(9):6120-6142. doi: 10.1007/s12010-025-05339-5.
Xinyue Hao  1 ,  Xiaoning Song  1 ,  Jing Ren  1 ,  Olayemi Eyituoyo Dudu  2 ,  Jingya Jiang  1 ,  Jianhua Zeng  1 ,  Song Wang  3 ,  Huaxi Yi  1 ,  Lanwei Zhang  1  4 ,  Pimin Gong  5  6
Affiliations
  • 1. College of Food Science and Engineering, Ocean University of China, Qingdao, 266000, Shandong Province, China.
  • 2. Department of Food Science and Technology, Bells University of Technology, Ota, Ogun State, Nigeria.
  • 3. Qingdao Shangde Biotech Co., Ltd, Qingdao, 266,000, China.
  • 4. Inner Mongolia National Center of Technology Innovation for Dairy, Hohhot, 150,100, China.
  • 5. College of Food Science and Engineering, Ocean University of China, Qingdao, 266000, Shandong Province, China. [email protected].
  • 6. Inner Mongolia National Center of Technology Innovation for Dairy, Hohhot, 150,100, China. [email protected].
PMID: 40650681 DOI: 10.1007/s12010-025-05339-5
Abstract

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.

Keywords
Lactobacillus delbrueckii subsp. bulgaricus; Casein hydrolysate; High-density culture; Lactic acid stress; SDG 2.
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