Process for the enantioselective enzymatic reduction of intermediates

A process for the enantioselective enzymatic reduction of a keto compound of general formula I

• wherein R represents a protective group for amino functions and X═—Cl, —CN, —OH, Br, F, to the hydroxy compound of general formula II (R,S-compound)
• wherein R and X have the same meaning as in formula I,
• with the keto compound being reduced with an oxidoreductase in the presence of a cofactor, characterized in that the oxidoreductase
• a) comprises an amino acid sequence according to SEQ ID NO:1, SEQ ID No 2, SEQ ID No3 or SEQ ID No 4, or
• b) comprises an amino acid sequence in which at least 65% of the amino acids are identical to those of amino acid sequences SEQ ID NO:1, SEQ ID No 2 or SEQ ID No3, SEQ ID No 4, or
• c) comprises an amino acid sequence in which at least 72% of the amino acids are identical to those of amino acid sequences SEQ ID NO:1, SEQ ID No 2 or SEQ ID No3, SEQ ID No 4, or
• d) is encoded by the nucleic acid sequence SEQ ID NO:16, SEQ ID No 17, SEQ ID No 18, SEQ ID No 19, or
• e) is encoded by a nucleic acid sequence which hybridizes to SEQ ID NO:16, SEQ ID No 17, SEQ ID No 18, SEQ ID No 19 under stringent conditions, or
• f) has a length of from no to 260 amino acids and comprises one or several of the partial sequences selected from the group consisting of sequences SEQ ID NO:31 to SEQ ID NO:51 and reduces the compound of formula Ito the compound of formula II.

A process for the enantioselective enzymatic reduction of a keto compound of general formula I

• wherein R represents a protective group for amino functions and X═—Cl, —CN, —OH, Br, F,
• to the hydroxy compound of general formula III (S,S-compound),
• wherein R and X have the same meaning as in formula I,
• with the keto compound being reduced with an oxidoreductase in the presence of a cofactor, characterized in that the oxidized cofactor NAD or NADP formed is regenerated continuously by oxidation of a secondary alcohol of general formula RXRYCHOH, wherein RX, RY independently represent hydrogen, a branched or unbranched C1-C8-alkyl group and Ctotal≧3.

A process for the enantioselective enzymatic reduction of a keto compound of general formula I

• wherein R represents a protective group for amino functions and X═−Cl, —CN, —OH, Br, F,
• to the hydroxy compound of general formula III (S,S-compound),
• wherein R and X have the same meaning as in formula I,
• with the keto compound being reduced with an oxidoreductase in the presence of a cofactor, characterized in that the oxidoreductase
• a) comprises an amino acid sequence according to SEQ ID NO:5, SEQ ID No 6, SEQ ID No7, SEQ ID No 8, SEQ ID No9, SEQ ID No10, SEQ ID No 11, SEQ ID No12, SEQ ID No13, SEQ ID No14, SEQ ID No15, or
• b) comprises an amino acid sequence in which at least 65% of the amino acids are identical to those of the amino acid sequences according to SEQ ID NO:5, SEQ ID No 6, SEQ ID No7, SEQ ID No 8, SEQ ID No9, SEQ ID No10, SEQ ID No11, SEQ ID No 12, SEQ ID No13, SEQ ID No14, SEQ ID No15, or
• c) is encoded by the nucleic acid sequence SEQ ID NO:20, SEQ ID No 21, SEQ ID No22, SEQ ID No 23, SEQ ID No24, SEQ ID No25, SEQ ID No26, SEQ ID No27, SEQ ID No28, SEQ ID No29 or SEQ ID No30, or
• d) is encoded by a nucleic acid sequence which hybridizes to SEQ ID NO:20, SEQ ID No 21, SEQ ID No22, SEQ ID No 23, SEQ ID No24, SEQ ID No25, SEQ ID No26, SEQ ID No27, SEQ ID No28, SEQ ID No29 or SEQ ID No30 under stringent conditions, or
• e) has a length of from 220 to 260 amino acids and comprises one or several of the partial sequences selected from the group consisting of sequences SEQ ID NO:31 to SEQ ID NO:66 and reduces the compound of formula I to the compound of formula III.