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

Álvarez García, Elisa and Alegre Cebollada, Jorge and Batanero Cremades, Eva and Monedero, Vicente and Pérez Martínez, Gaspar and García Fernández, Rosa and Gavilanes, José G. and Martínez del Pozo, Álvaro (2007) Lactococcus lactis as a vehicle for the heterologous expression of fungal ribotoxin variants with reduced IgE-binding affinity. Journal of Biotechnology, 134 . pp. 1-8. ISSN 1873-4863

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Abstract

Fungal 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.


Item Type:Article
Uncontrolled Keywords:alfa-Sarcin; Asp f 1; Ribonuclease; Probiotic
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Biotechnology
Medical sciences > Biology > Molecular biology
ID Code:7749
Deposited On:26 Mar 2008
Last Modified:06 Feb 2014 07:55

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