%0 Journal Article
%A Álvarez García, Elisa
%A Alegre Cebollada, Jorge
%A Batanero Cremades, Eva
%A Monedero, Vicente
%A Pérez Martínez, Gaspar
%A García Fernández, Rosa Ana
%A Gavilanes, José G.
%A Martínez del Pozo, Álvaro
%T Lactococcus lactis as a vehicle for the heterologous expression of fungal ribotoxin variants with reduced IgE-binding affinity
%D 2007
%@ 1873-4863
%U https://hdl.handle.net/20.500.14352/52894
%X Fungal ribotoxins are a family of extracellular ribonucleases which inhibit protein biosynthesis by inactivating the ribosomes. This inactivationresults in the induction of cell death by apoptosis. Ribotoxins show antitumoral properties based on their ability to cross the membrane of sometransformed 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 itsmajor 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 formwhen the extracellular medium employed was buffered at pH values around 8.0. Strains producing the wild-type natural alfa-sarcin were proved to beinnocuous when administered intragastrically to mice for a period of 14 days. Overall, the results presented are discussed in terms of its potentialapplication as a vehicle of oral delivery of hypoallergenic variants as well as a starting point to approach the design of strategies to accomplish thesafe delivery of these proteins as antitumoral agents.
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