Enzyme Technology in Biocatalytic Reduction

In the first approach, one enzyme is needed to convert both substrate (ketone) and co-substrate (alcohol). The second alcohol needs to afford a ketone which can be easily removed by distillation, e.g. acetone, to drive the reduction to completion. For most alcohol-dehydrogenases, however, the enzyme can only 

One of the prominent industrial bioreduction processes, run by cofactor regeneration, is performed by leucine dehydrogenase. This enzyme can catalyze the reductive amination of trimethylpyruvic acid, using ammonia (see Fig. 3.45). For this process the cofactor regeneration takes place by using formate as the reductant and formate dehydrogenase as the second enzyme. The advantage of 

An example of glucose coupled ketone reduction is the continuous mode reduction using whole (dead) cells of Lactobacillus kefir for the enantioselective reduction of 2,5-hexanedione to (2R,5R)-hexanediol - a popular chiral ligand for 

Another example for biocatalytic reduction using glucose as the reductant, is the production of (R)-ethyl-4,4,4-trifluoro-3-hydroxybutanoate by Lonza [130]. It is a building block for pharmaceuticals such as Befloxatone, an anti-depressant monoamine oxidase-A inhibitor from Synthelabo. The process uses whole cells of Escheria coli that contain two plasmids. One carries an aldehyde reductase 

When the enantioselective reduction of ethyl 4-chloroacetoacetate was carried out with alcohol dehydrogenase from Candida parapsilosis, the other enantiomer was produced ethyl (P)-4-chloro-3-hydroxybutanoate [134]. This product is a key intermediate in a synthesis of (R)-carnitine. In this case a substrate coupled approach was chosen. The enzyme also has a strong oxidation activity for 2-propanol, which was therefore selected as the cosubstrate. The situation is depicted in Fig. 3.50. Under optimized conditions, the yield of (R)-ethyl-4-chloro-3-hydroxy-butanoate reached 36.6 g L-1 ( 99% ee, 95% yield) on a 30 L scale. 

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