Alcohol dehydrogenase (ADH)

Sandra Forbes

Product Manager

Dehydrogenases function as enzymes responsible for oxidizing and reducing carbonyl groups, particularly alcohols. These enzymes primarily rely on NAD(P)H for their activity. In the reduction process of aldehydes and ketones, baker yeast is frequently employed.

When it comes to reductions involving isolated enzymes, the cofactor NAD(P)H - serving as the hydride donor - must be used stoichiometrically or regenerated through the in situ reduction of NAD(P)+. This is due to the high costs associated with the reaction.

One method for recycling NAD(P)H involves the utilization of a second enzyme along with a suitable substrate that can be oxidized. Some examples of such combinations include glucose with glucose dehydrogenases, glucose-6-phosphate with glucose-6-phosphate dehydrogenases, and alcohol with alcohol dehydrogenases.

Formate dehydrogenase is frequently employed as an enzyme to oxidize formic acid into CO2, facilitating the recovery of NADH from NAD. While this approach is commonly utilized in the reduction of carbonyl groups to alcohols and amines, it is not suitable for the recovery of NADPH.

Recent Literature

During the asymmetric biocatalytic reduction of ketones in a biphasic reaction media, with cofactor regeneration occurring in situ, both enzymes - ADH and FDH - maintain their stability. For ketones that are poorly water-soluble, the reductions were conducted using substrate concentrations exceeding 10 mM. This resulted in the formation of alcohols with excellent conversions and high enantioselectivity.

H. Groeger, W. Hummel, S. Buchholz, K. Drauz, T. V. Nguyen, C. Rollmann, H. Huesken, K. Abokitse, Org. Lett., 2003, 5, 173-176.

https://pubs.acs.org/doi/10.1021/ol0272139

Through the meticulous selection of suitable enzymes, specifically alcohol dehydrogenases (ADH) and cofactor recycling enzymes, NADH cofactor recycling can be effectively executed in the presence of NADP+ recycling. This enables the overall (R)- or (S)-selective deracemisations of sec-alcohols or stereoinversion, offering a potential "green" alternative to the chemically intensive Mitsunobu inversion process.

C. V. Voss, C. C. Gruber, K. Faber, T. Knaus, P. Macheroux, W. Kroutil, J. Am. Chem. Soc., 2008, 130, 13969-13972.

https://doi.org/10.1021/ja804816a

Sphingomonas paucimobilis NCIMB 8195 exhibits remarkable catalytic activity in efficiently deracemizing a diverse array of secondary alcohols, achieving yields of up to 90% for the (R)-alcohol. Notably, during each biotransformation process, corresponding ketones were formed at varying levels, suggestive of stereoinversion of the (S)-alcohol occurring through sequential oxidation and reduction reactions.

G. R. Allan, A. J. Carnell, J. Org. Chem., 2001, 66, 6495-6497.

https://doi.org/10.1021/jo015770n

Quoted from: https://www.organic-chemistry.org/chemicals/reductions/alcoholdehydrogenase-adh.shtm

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