Efficient and enantioselective catalysis by the semisynthetic peroxidase seleno-subtilisin

Abstract

By selective modification of serine 221 in the active site, the preceding protease subtilisin carlsberg gained peroxidase activity which was subsequently utilized for the enantioselective reduction of hydroperoxides. Thus, semisynthetic seleno-subtilisin selectively catalyzed the kinetic resolution of four racemic alkyl aryl hydroperoxides p-R 2-C 6H 4CH(OOH)R 1 (R 1=CH 3, CH 2OH, CH(CH 3) 2; R 2=H, Cl). The enantiomeric distribution of all products was determined and kinetic parameters were evaluated, indicating seleno-subtilisin as the first semisynthetic enzyme with catalytic efficiency comparable to native enzymes and good enantioselectivity. In order to facilitate further studies, structural motifs responsible for enantioselectivity and efficiency of catalysis were outlined in the discussion, thus providing a rational basis for the selection of suitable substrates.