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  • Jefferson Adams

    Can Gluten Degrading Enzymes Help Celiac Disease Sufferers?

    Jefferson Adams
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    Reviewed and edited by a celiac disease expert.

      Researchers identify food-grade subtilisins as gluten-degrading enzymes that might help treat celiac disease.


    Image: CC--frederic glorieux
    Caption: Image: CC--frederic glorieux

    Celiac.com 12/26/2016 - Could gluten-degrading enzymes offer a better future for celiac patients? Rothia mucilaginosa is an oral microbial colonizer that can break down proline- and glutamine-rich proteins present in wheat, barley, and rye that contain the immunogenic sequences that drive celiac disease. A team of researchers recently set out to isolate and identify the enzymes and evaluate their potential as novel enzyme therapeutics for celiac disease.

    The research team included G Wei, N Tian, R Siezen, D Schuppan, and EJ Helmerhorst. They are variously affiliated with the Department of Molecular and Cell Biology at the Henry M. Goldman School of Dental Medicine in Boston, Massachusetts; the Bacterial Genomics Group, Center for Molecular and Biomolecular Informatics at Radboud University Medical Centre, Nijmegen, the Netherlands; the Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and with the Institute of Translational Immunology and Research Center for Immunology, University Medical Center, Johannes-Gutenberg-University, Mainz, Germany.



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    They first extracted and separated membrane-associated R. mucilaginosa proteins using DEAE chromatography. They tracked enzyme activities using paranitroanilide-derivatized and fluorescence resonance energy transfer (FRET) peptide substrates, and by gliadin zymography. They determined epitope elimination in R5 and G12 ELISAs. They identified gliadin-degrading Rothia enzymes by LC-ESI-MS/MS as hypothetical proteins ROTMU0001_0241 (C6R5V9_9MICC), ROTMU0001_0243 (C6R5W1_9MICC), and ROTMU0001_240 (C6R5V8_9MICC).

    The Rothia subtilisins and two subtilisins from Bacillus licheniformis, subtilisin A and the food-grade Nattokinase, efficiently degraded the immunogenic gliadin-derived 33-mer peptide and the immunodominant epitopes recognized by the R5 and G12 antibodies.

    This study identified Rothia and food-grade Bacillus subtilisins as promising new candidates for enzyme therapeutics in celiac disease. To do this, the team cleaved succinyl-Ala-Ala-Pro-Phe-paranitroanilide, a substrate for subtilisin with Pro in the P2 position, as in Tyr-Pro-Gln and Leu-Pro-Tyr in gluten, which are also cleaved. Consistently, FRET substrates of gliadin immunogenic epitopes comprising Xaa-Pro-Xaa motives were rapidly hydrolyzed.

    They found that Rothia subtilisins and two subtilisins from Bacillus licheniformis, subtilisin A and the food-grade Nattokinase, efficiently degraded the immunogenic gliadin-derived 33-mer peptide and the immunodominant epitopes recognized by the R5 and G12 antibodies.

    Rothia and food-grade Bacillus subtilisins show promise for development as enzyme therapies for celiac disease.

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  • About Me

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.


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