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Lactococcus lactis as a vehicle for the heterologous expression of fungal ribotoxin variants with reduced IgE-binding affinity

dc.contributor.authorÁlvarez García, Elisa
dc.contributor.authorAlegre Cebollada, Jorge
dc.contributor.authorBatanero Cremades, Eva
dc.contributor.authorMonedero, Vicente
dc.contributor.authorPérez Martínez, Gaspar
dc.contributor.authorGarcía Fernández, Rosa
dc.contributor.authorGavilanes, José G.
dc.contributor.authorMartínez del Pozo, Álvaro
dc.date.accessioned2023-06-20T12:58:07Z
dc.date.available2023-06-20T12:58:07Z
dc.date.issued2007-06-25
dc.description.abstractFungal ribotoxins are a family of extracellular ribonucleases which inhibit protein biosynthesis by inactivating the ribosomes. This inactivation results in the induction of cell death by apoptosis. Ribotoxins show antitumoral properties based on their ability to cross the membrane of some transformed cells. Unfortunately, they also show an unspecific cytotoxicity which has greatly impaired their potential clinical uses. Alfa-sarcin, produced by Aspergillus giganteus, is the best-characterized ribotoxin. Asp f 1, another ribotoxin produced by A. fumigatus, is indeed one of its major allergens. In this work, the Lactococcus lactis MG1363 strain has been engineered to produce and secrete not only wild-type Asp f 1 and -sarcin but also three different mutants with reduced cytotoxicity and/or IgE-binding affinity. The proteins were secreted in native and active form when the extracellular medium employed was buffered at pH values around 8.0. Strains producing the wild-type natural alfa-sarcin were proved to be innocuous when administered intragastrically to mice for a period of 14 days. Overall, the results presented are discussed in terms of its potential application as a vehicle of oral delivery of hypoallergenic variants as well as a starting point to approach the design of strategies to accomplish the safe delivery of these proteins as antitumoral agents.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/7749
dc.identifier.doi10.1016/j.jbiotec.2007.12.011
dc.identifier.issn1873-4863
dc.identifier.officialurlhttp://www.elsevier.com/wps/find/journaldescription.cws_home/505515/description#description
dc.identifier.urihttps://hdl.handle.net/20.500.14352/52894
dc.journal.titleJournal of Biotechnology
dc.language.isospa
dc.page.final8
dc.page.initial1
dc.rights.accessRightsopen access
dc.subject.keywordalfa-Sarcin
dc.subject.keywordAsp f 1
dc.subject.keywordRibonuclease
dc.subject.keywordProbiotic
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmBiotecnología
dc.subject.ucmBiología molecular (Biología)
dc.subject.unesco2302 Bioquímica
dc.subject.unesco3399 Otras Especialidades Tecnológicas
dc.subject.unesco2415 Biología Molecular
dc.titleLactococcus lactis as a vehicle for the heterologous expression of fungal ribotoxin variants with reduced IgE-binding affinity
dc.typejournal article
dc.volume.number134
dspace.entity.typePublication
relation.isAuthorOfPublication862e3690-e517-4123-8c8f-41ed416ffe4c
relation.isAuthorOfPublication.latestForDiscovery862e3690-e517-4123-8c8f-41ed416ffe4c
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