Heterologous protein export in Lactococcus lactis: development of molecular tools and applications.

The GRAS (for Generally Regarded As Safe) bacterium, Lactococcus lactis, is a good candidate to produce heterologous proteins of vaccinal, medical or technological interest. The export (secretion or cell wall anchoring) of su ch proteins would allow a direct contact between the protein and its target and therefore would be a better mode of production than intracellular prod uction. To develop heterologous protein export systems in L. lactis, we use d the staphylococcal nuclease. Three major results were obtained in L, lact is: (i) a synthetic propeptide has been identified which enhances secretion efficiency of heterologous proteins; (ii) a fusion protein has been design ed which allows to target a protein of interest to three cellular localizat ions (secreted, anchored or intracellular); and (iii) new lactococcal expor t signals have been identified. These tools are being used to construct L. lactis strains able to export viral antigens and technological enzymes.