Heterologous production of natural and non-cytotoxic variants of fungal ribotoxins in Lactococcus lactis

Abstract

L. lactis is a GRAS (“Generally Regarded As Safe”) gram-positive bacterium that does not colonize the digestive tract and has been proposed as a potential in vivo vaccine or therapeutic agent carrier. α-sarcin (αS) is an antitumoral toxic protein that is very similar to Asp f 1, the major allergen of Aspergillus fumigatus. We have cloned and produced extracellularly in L. lactis several variants of αS and Asp f 1, as well as their natural versions. These include: both wild-type proteins, αS H137Q (a properly folded catalytically inactive and non toxic variant of αS), αS Δ(7-22) and Asp f 1 Δ(7-22) (catalytically active but non toxic variants with reduced IgE responses). At this moment, fungal allergic and colon cancer mice models are being developed in order to test the potential therapeutic effects of the different L. lactis strains produced.