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Generation of food-grade recombinant Lactobacillus casei delivering Myxococcus xanthus prolyl endopeptidase

Alvarez-Sieiro, P., Martin, M. C., Redruello, B., Del Rio, B., Ladero, V., Palanski, B. A., Khosla, C., Fernandez, M. & Alvarez, M. A., Aug-2014, In : Applied Microbiology and Biotechnology. 98, 15, p. 6689-6700 12 p.

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  • Generation of food-grade recombinant Lactobacillus casei delivering

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DOI

  • Patricia Alvarez-Sieiro
  • Maria Cruz Martin
  • Begoña Redruello
  • Beatriz Del Rio
  • Victor Ladero
  • Brad A Palanski
  • Chaitan Khosla
  • Maria Fernandez
  • Miguel A Alvarez

Prolyl endopeptidases (PEP) (EC 3.4.21.26), a family of serine proteases with the ability to hydrolyze the peptide bond on the carboxyl side of an internal proline residue, are able to degrade immunotoxic peptides responsible for celiac disease (CD), such as a 33-residue gluten peptide (33-mer). Oral administration of PEP has been suggested as a potential therapeutic approach for CD, although delivery of the enzyme to the small intestine requires intrinsic gastric stability or advanced formulation technologies. We have engineered two food-grade Lactobacillus casei strains to deliver PEP in an in vitro model of small intestine environment. One strain secretes PEP into the extracellular medium, whereas the other retains PEP in the intracellular environment. The strain that secretes PEP into the extracellular medium is the most effective to degrade the 33-mer and is resistant to simulated gastrointestinal stress. Our results suggest that in the future, after more studies and clinical trials, an engineered food-grade Lactobacillus strain may be useful as a vector for in situ production of PEP in the upper small intestine of CD patients.

Original languageEnglish
Pages (from-to)6689-6700
Number of pages12
JournalApplied Microbiology and Biotechnology
Volume98
Issue number15
Publication statusPublished - Aug-2014
Externally publishedYes

    Keywords

  • Celiac disease, Gluten, Prolyl endopeptidase, Myxococcus xanthus, Heterologous expression, Lactobacillus casei, LACTIC-ACID BACTERIA, AGGREGATION-PROMOTING FACTOR, SITE-SPECIFIC RECOMBINATION, CELIAC-DISEASE, GLUTEN SENSITIVITY, GLIADIN PEPTIDES, MOUSE MODEL, IN-VITRO, SPRUE, EXPRESSION

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