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Asymmetric Reduction of α‐Keto Esters with Thermus thermophilus NADH‐Dependent Carbonyl Reductase using Glucose Dehydrogenase and Alcohol Dehydrogenase for Cofactor Regeneration
Author(s) -
Pennacchio Angela,
Giordano Assunta,
Rossi Mosè,
Raia Carlo A.
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201100107
Subject(s) - chemistry , alcohol dehydrogenase , cofactor , thermus thermophilus , dehydrogenase , yield (engineering) , reductase , alcohol , alcohol oxidoreductase , nad+ kinase , stereochemistry , biochemistry , enzyme , escherichia coli , materials science , metallurgy , gene
The enantioselective synthesis of methyl ( R )‐mandelate and methyl ( R )‐ o ‐chloromandelate was investigated using an NADH‐dependent carbonyl reductase from Thermus thermophilus (TtADH) and, separately, archaeal glucose dehydrogenase and Bacillus stearothermophilus alcohol dehydrogenase (BsADH) for NADH regeneration. Optimal reaction times and substrate concentrations in the absence and presence of organic solvents were determined. The enantiofacial selectivity of TtADH was shown to be inversely proportional to the hydrophobicity of the short‐chain linear alcohols employed as co‐substrates of the bacillar ADH. The bioreduction of methyl benzoylformate yielded the ( R )‐alcohol with a 77 % yield ( ee = 96 %) using glucose dehydrogenase and glucose, and 81 % yield ( ee = 94 %) applying BsADH and ethanol. The bioreduction of methyl o ‐chlorobenzoylformate yielded the halogenated ( R )‐alcohol with 95 % and 92 % ee , and 62 % and 78 % yield using glucose dehydrogenase and BsADH, respectively.