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Advanced Insights into Catalytic and Structural Features of the Zinc-Dependent Alcohol Dehydrogenase from Thauera aromatica

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JournalChembiochem
DateAccepted/In press - 6 May 2022
DateE-pub ahead of print (current) - 14 Jun 2022
Number of pages12
Early online date14/06/22
Original languageEnglish

Abstract

The asymmetric reduction of ketones to chiral hydroxyl compounds by alcohol
dehydrogenases (ADHs) is an established strategy for the provision of valuable
precursors for fine chemicals and pharmaceutics. However, most ADHs favor linear aliphatic and aromatic carbonyl compounds, and suitable biocatalysts with preference for cyclic ketones and diketones are still scarce. Among the few candidates, the alcohol dehydrogenase from Thauera aromatica (ThaADH) stands out with a high activity for the reduction of the cyclic α-diketone 1,2-cyclohexanedione to the corresponding α-hydroxy ketone. This study elucidates catalytic and structural features of the enzyme. ThaADH showed a remarkable thermal and pH stability as well as stability in the presence of polar solvents. A thorough description of the substrate scope combined with the resolution and description of the crystal structure, demonstrated a strong preference of ThaADH for cyclic α-substituted cyclohexanones, and indicated structural
determinants responsible for the unique substrate acceptance.

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© 2022The Authors

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