Extracellular secretion of a recombinant therapeutic peptide by Bacillus halodurans utilizing a modified flagellin type III secretion system.

Background: Through modification of the flagellin type III secretion pathway of Bacillus halodurans heterologous peptides could be secreted into the medium as flagellin fusion monomers. The stability of the secreted monomers was significantly enhanced through gene-targeted inactivation of host cell extracellular proteases. In evaluating the biotechnological potential of this extracellular secretion system an anti-viral therapeutic peptide, Enfuvirtide, was chosen.

Impact of inactivated extracellular proteases on the modified flagellin type III secretion pathway of Bacillus halodurans.

The flagellin type III secretion pathway of Bacillus halodurans BhFC01 (Deltahag) was modified by the inactivation of fliD. An in-frame flagellin gene fusion polypeptide construct was expressed, and the heterologous peptides were secreted as flagellin fusion monomers. The stability of the secreted monomers was significantly enhanced through gene-targeted inactivation of extracellular proteases.