Frontiers in Microbiology (May 2024)

Effect of folA gene in human breast milk-derived Limosilactobacillus reuteri on its folate biosynthesis

  • Yu Jiang,
  • Yu Jiang,
  • Yu Jiang,
  • Xianping Li,
  • Xianping Li,
  • Wei Zhang,
  • Wei Zhang,
  • Yadong Ji,
  • Yadong Ji,
  • Kai Yang,
  • Kai Yang,
  • Lu Liu,
  • Lu Liu,
  • Minghui Zhang,
  • Minghui Zhang,
  • Weicang Qiao,
  • Weicang Qiao,
  • Junying Zhao,
  • Junying Zhao,
  • Mengjing Du,
  • Mengjing Du,
  • Xiaofei Fan,
  • Xiaofei Fan,
  • Xingfen Dang,
  • Xingfen Dang,
  • Huo Chen,
  • Huo Chen,
  • Tiemin Jiang,
  • Lijun Chen,
  • Lijun Chen,
  • Lijun Chen

DOI
https://doi.org/10.3389/fmicb.2024.1402654
Journal volume & issue
Vol. 15

Abstract

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IntroductionFolate supplementation is crucial for the human body, and the chemically synthesized folic acid might have undesirable side effects. The use of molecular breeding methods to modify the genes related to the biosynthesis of folate by probiotics to increase folate production is currently a focus of research.MethodsIn this study, the folate-producing strain of Limosilactobacillus reuteri B1-28 was isolated from human breast milk, and the difference between B1-28 and folA gene deletion strain ΔFolA was investigated by phenotyping, in vitro probiotic evaluation, metabolism and transcriptome analysis.ResultsThe results showed that the folate producted by the ΔFolA was 2–3 folds that of the B1-28. Scanning electron microscope showed that ΔFolA had rougher surface, and the acid-producing capacity (p = 0.0008) and adhesion properties (p = 0.0096) were significantly enhanced than B1-28. Transcriptomic analysis revealed that differentially expressed genes were mainly involved in three pathways, among which the biosynthesis of ribosome and aminoacyl-tRNA occurred in the key metabolic pathways. Metabolomics analysis showed that folA affected 5 metabolic pathways, involving 89 different metabolites.DiscussionIn conclusion, the editing of a key gene of folA in folate biosynthesis pathway provides a feasible pathway to improve folate biosynthesis in breast milk-derived probiotics.

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