STRAIGHTFORWARD DEVELOPMENT OF STEREOSELECTIVE BIOCATALYSTS - FROM DETERGENT TO SEMISYNTHETIC PEROXIDASE SELENO-SUBTILISIN

The industrially produced serine protease subtilisin was chemically co nverted into a peroxidase by selective modification of the active site serine 221 into selenocystein. The synthesis of seleno-subtilisin was up-scaled to gram-scale and the semisynthetic peroxidase utilized for the enantioselective reduction of racemic alkyl aryl hydroperoxides. The enantiomeric distribution of the products was determined (up to 98 % ee) and the enantioselectivity rationalized by comparison of the hyd roperoxides to corresponding subtilisin substrates. Substrate affinity of several substituted 1-arylethyl hydroperoxides to seleno-subtilisi n was reasonable in comparison to corresponding aryl boronic acid inhi bitors of subtilisin. Kinetic studies of the semisynthetic seleno-subt ilisin revealed a catalytic efficiency comparable to native horseradis h peroxidase. (C) 1998 Elsevier Science B.V. All rights reserved.