In conclusion, we employed crystal contact engineering to generate CLECs of HheG with chemoselective cross-linking at predefined cross-linking sites. To this end, HheG variant D114C was generated for stable cross-linking with the thiol-specific cross-linker BMOE. In contrast to CLECs generated with the commonly used cross-linker glutaraldehyde, this approach yielded selective cross-linking at welldefined sites without compromising enzyme activity. The resulting CLECs not only displayed significantly higher stability regarding temperature, pH and co-solvent concentrations compared to the soluble enzyme, but also enabled the repetitive use of HheG in the azidolysis of various epoxide substrates (up to 21 days as shown for the conversion of cyclohexene oxide). Overall, those CLECs represent an important first step towards a potential future application of HheG in industrial settings.