Oxynitrilases: From cyanogenesis to asymmetric synthesis

Oxynitrilases are enzymes which catalyse the formation and cleavage of cyan ohydrins. The cyanohydrin formation reaction proceeds by stereoselective ad dition of hydrogen cyanide to aldehydes or ketones to give enantiopure alph a-hydroxynitriles. This simple method of C-C bond formation has become a pr omising method to obtain a number of biologically active compounds. Cyanohy drin fission plays an important role in nature and is involved in plant def ence where hydrogen cyanide is liberated upon plant damage. Among the known oxynitrilases only the (R)-oxynitrilase from Prunus amygdalus and the (S)- oxynitrilases from Hevea brasiliensis and Manihot esculenta are available i n sufficient quantities which allow cyanohydrin formation on a larger scale . Prunus amygdalus oxynitrilase can easily be isolated from natural sources (bitter almond bran) and for two (S)-oxynitrilases functional overexpressi on allows their production in sufficient amounts for broad preparative appl ications. The three dimensional structure of the (S)-oxynitrilase from Heve a brasiliensis has been determined, and suggestions concerning the reaction mechanism have been discussed. Several procedures employing oxynitrilases have been developed to date which enable cyanohydrin formation on a prepara tive scale, particularly the use of buffer solutions as the reaction medium , organic solvents with immobilised enzymes, as well as biphasic reaction s ystems. Possible follow up reactions of the generated hydroxy and nitrile f unctionality, as well as the conversion of unsaturated cyanohydrins into va luable asymmetric compounds are outlined.