Bioreductions Catalyzed by an Alcohol Dehydrogenase in Non-aqueous Media

• Published in: ChemCatChem Vol. 6; no. 4; pp. 973 - 976
• Main Authors: Kara, Selin, Spickermann, Dominik, Weckbecker, Andrea, Leggewie, Christian, Arends, Isabel W. C. E., Hollmann, Frank
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.04.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Alcohol; Alcohol dehydrogenase; alcohol dehydrogenases; biotransformations; Boiling points; Butanediol; Butanol; Dehydrogenases; organic media; Reagents; reduction; smart cosubstrates; Substrates; Toluene
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.201300841

Highly productive biocatalytic reductions were established using an isolated alcohol dehydrogenase (ADH) under water‐deficient conditions. First, a solvent‐free system was evaluated for the reduction of 2‐butanone catalyzed by ADH evo‐1.1.200 promoted by the “smart cosubstrate” 1,4‐butanediol. ADH evo‐1.1.200 excelled by its activity and stability under high reagent concentrations and hence was the enzyme of choice. However, conversion of 2‐butanone was limited to <1 % in 10 days under the solvent‐free conditions. Therefore, water‐immiscible organic solvents were evaluated whereby the highest conversions were achieved in MTBE and toluene. MTBE was chosen as its different boiling point compared to other reaction components (e.g., 2‐butanone, 2‐butanol, diol cosubstrate, and lactone coproduct) would simplify the downstream processing. Further on, by tuning substrate loading, the productivity of the ADH evo‐1.1.200 was successfully increased to a turnover number (TON) of 64 000. Practical water‐deficient enzymology for bioreductions: The use of alcohol dehydrogenases (ADHs) in neat substrates and in water‐immiscible organic solvents is explored. The ADH evo‐1.1.200 excelled by its high stability, as it showed significant catalytic activity over days. Reductions are coupled with the “smart cosubstrate” 1,4‐butanediol; hence, excess amounts of reductants are avoided.