E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance

Abstract Gluten proteins are the causative agent of Celiac Disease (CD), a life-long food intolerance characterized by an autoimmune enteropathy. Inadvertent gluten exposure is frequent even in celiac patients complying with a gluten-free diet, and the supplementation of exogenous gluten-digestive e...

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Autores principales:	Linda Cavaletti, Anna Taravella, Lucia Carrano, Giacomo Carenzi, Alessandro Sigurtà, Nicola Solinas, Salvatore De Caro, Luigia Di Stasio, Stefania Picascia, Mariavittoria Laezza, Riccardo Troncone, Carmen Gianfrani, Gianfranco Mamone
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2473102e65d44424bb0246eb61f00842
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spelling	oai:doaj.org-article:2473102e65d44424bb0246eb61f008422021-12-02T15:09:53ZE40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance10.1038/s41598-019-48299-72045-2322https://doaj.org/article/2473102e65d44424bb0246eb61f008422019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48299-7https://doaj.org/toc/2045-2322Abstract Gluten proteins are the causative agent of Celiac Disease (CD), a life-long food intolerance characterized by an autoimmune enteropathy. Inadvertent gluten exposure is frequent even in celiac patients complying with a gluten-free diet, and the supplementation of exogenous gluten-digestive enzymes (glutenases) is indeed a promising approach to reduce the risk of dietary gluten boost. Here we describe Endopeptidase 40, a novel glutenase discovered as secreted protein from the soil actinomycete Actinoallomurus A8, and its recombinant active form produced by Streptomyces lividans TK24. E40 is resistant to pepsin and trypsin, and active in the acidic pH range 3 to 6. E40 efficiently degrades the most immunogenic 33-mer as well as the whole gliadin proteins, as demonstrated by SDS-PAGE, HPLC, LC-MS/MS, and ELISA. T lymphocytes from duodenal biopsies of celiac patients showed a strongly reduced or absent release of IFN-γ when exposed to gluten digested with E40. Data in gastrointestinal simulated conditions suggest that no toxic peptides are freed during gluten digestion by E40 into the stomach to enter the small intestine, thus counteracting the intestinal inflammatory cascade to occur in CD patients. E40 is proposed as a novel candidate in Oral Enzymatic Therapy for the dietary management of gluten toxicity.Linda CavalettiAnna TaravellaLucia CarranoGiacomo CarenziAlessandro SigurtàNicola SolinasSalvatore De CaroLuigia Di StasioStefania PicasciaMariavittoria LaezzaRiccardo TronconeCarmen GianfraniGianfranco MamoneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linda Cavaletti Anna Taravella Lucia Carrano Giacomo Carenzi Alessandro Sigurtà Nicola Solinas Salvatore De Caro Luigia Di Stasio Stefania Picascia Mariavittoria Laezza Riccardo Troncone Carmen Gianfrani Gianfranco Mamone E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
description	Abstract Gluten proteins are the causative agent of Celiac Disease (CD), a life-long food intolerance characterized by an autoimmune enteropathy. Inadvertent gluten exposure is frequent even in celiac patients complying with a gluten-free diet, and the supplementation of exogenous gluten-digestive enzymes (glutenases) is indeed a promising approach to reduce the risk of dietary gluten boost. Here we describe Endopeptidase 40, a novel glutenase discovered as secreted protein from the soil actinomycete Actinoallomurus A8, and its recombinant active form produced by Streptomyces lividans TK24. E40 is resistant to pepsin and trypsin, and active in the acidic pH range 3 to 6. E40 efficiently degrades the most immunogenic 33-mer as well as the whole gliadin proteins, as demonstrated by SDS-PAGE, HPLC, LC-MS/MS, and ELISA. T lymphocytes from duodenal biopsies of celiac patients showed a strongly reduced or absent release of IFN-γ when exposed to gluten digested with E40. Data in gastrointestinal simulated conditions suggest that no toxic peptides are freed during gluten digestion by E40 into the stomach to enter the small intestine, thus counteracting the intestinal inflammatory cascade to occur in CD patients. E40 is proposed as a novel candidate in Oral Enzymatic Therapy for the dietary management of gluten toxicity.
format	article
author	Linda Cavaletti Anna Taravella Lucia Carrano Giacomo Carenzi Alessandro Sigurtà Nicola Solinas Salvatore De Caro Luigia Di Stasio Stefania Picascia Mariavittoria Laezza Riccardo Troncone Carmen Gianfrani Gianfranco Mamone
author_facet	Linda Cavaletti Anna Taravella Lucia Carrano Giacomo Carenzi Alessandro Sigurtà Nicola Solinas Salvatore De Caro Luigia Di Stasio Stefania Picascia Mariavittoria Laezza Riccardo Troncone Carmen Gianfrani Gianfranco Mamone
author_sort	Linda Cavaletti
title	E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
title_short	E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
title_full	E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
title_fullStr	E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
title_full_unstemmed	E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
title_sort	e40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/2473102e65d44424bb0246eb61f00842
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E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance

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