A Dynamic Loop in Halohydrin Dehalogenase HheG Regulates Activity and Enantioselectivity in Epoxide Ring Opening.

ABSTRACT: Halohydrin dehalogenase HheG and its homologues are remarkable enzymes for the efficient ring opening of sterically demanding internal epoxides using a variety of nucleophiles. The enantioselectivity of the respective wild-type enzymes, however, is usually insufficient for application and frequently requires improvement by protein engineering. We herein demonstrate that the highly flexible N-terminal loop of HheG, comprising residues 39 to 47, has a tremendous impact on the activity as well as enantioselectivity of this enzyme in the ring opening of structurally diverse epoxide substrates. Thus, highly active and enantioselective HheG variants could be accessed through targeted engineering of this loop. In this regard, variant M45F displayed almost 10-fold higher specific activity than wil

SUBMITTER: Staar M 

PROVIDER: S-EPMC11536340 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature