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

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• 作者：Elisa &#xc1 ; lvarez-Garc&#xed ; a ; Jorge Alegre-Cebollada ; Eva Batanero ; Vicente Monedero ; Gaspar P&#xe9 ; rez-Mart&#xed ; nez ; Rosa Garc&#xed ; a-Fern&#xe1 ; ndez ; Jose G. Gavilanes ; &#xc1 ; lvaro Mart&#xed ; nez d
• 关键词：c="http ; //www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-Sarcin ; Asp f 1 ; Ribonuclease ; Probiotic
• 刊名：Journal of Biotechnology
• 出版年：2008
• 期刊代码：53_01681656
• 类别：imm
• 出版时间：20 March 2008
• 卷：134
• 期：1-2
• 页码：1-8
• 文件大小：663 K

摘要

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. c="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-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 c="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-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 c="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-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.