Sortase A from Staphylococcus aureus (SrtAstaph) has been exploited as a tool for generating site-specifically modified proteins for applications in therapeutics and biotechnology. While this approach to protein modification is promising, it is limited to installing modifications at the protein N- or C-termini. With the goal of circumventing this limitation, we are exploring sortase-mediated protein modifications involving internal amino acid residues. We have identified three sortase A homologs from Streptococcus suis, Streptococcus oralis, and Streptococcus pneumoniae for this purpose. The natural amine nucleophile for these enzymes is predicted to be the side chain of a lysine residue present in the cell wall precursor lipid II. This naturally results in the formation of isopeptide bonds on the bacterial cell surface. Here we present progress toward reproducing this reactivity in vitro.

Generating isopeptide bonds using sortase A homologs

251st National Meeting (2016)

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