Abstract 2232 Enzymatic Promiscuity of Thioether Crosslinking in Non-Native Peptide Architectures

PapB is a promiscuous radical S-adenosyl-L-methionine (rSAM) enzyme, distinguished by its ability to introduce thio(seleno)ether crosslinks into a wide array of substrates. Despite its versatility, the substrate range of PapB has not been fully explored, with previous research primarily focusing on its native Cys-X3-Asp thioether motif. The inherent redox stability of thioether crosslinks positions PapB as a promising tool for biotechnological applications. Our current study demonstrates PapB's capability to process both nested and in-line crosslinks across varying distances between each crosslinking site.