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

Frances Stark; Christoph Loderer; Mark Petchey; Gideon James Grogan; Marion Ansorge-Schumacher

doi:10.1002/cbic.202200149

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

Frances Stark, Christoph Loderer, Mark Petchey, Gideon James Grogan, Marion Ansorge-Schumacher

Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e202200149
Number of pages	12
Journal	Chembiochem
Early online date	14 Jun 2022
DOIs	https://doi.org/10.1002/cbic.202200149
Publication status	E-pub ahead of print - 14 Jun 2022

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10.1002/cbic.202200149Licence: CC BY

Advanced Insights into Catalytic and Structural Features of the Zinc‐Dependent Alcohol
© 2022The Authors
Final published version, 1.22 MBLicence: CC BY

Cite this

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

abstract = "The asymmetric reduction of ketones to chiral hydroxyl compounds by alcoholdehydrogenases (ADHs) is an established strategy for the provision of valuableprecursors 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 structuraldeterminants responsible for the unique substrate acceptance.",

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AU - Stark, Frances

AU - Loderer, Christoph

AU - Petchey, Mark

AU - Grogan, Gideon James

AU - Ansorge-Schumacher, Marion

PY - 2022/6/14

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AB - The asymmetric reduction of ketones to chiral hydroxyl compounds by alcoholdehydrogenases (ADHs) is an established strategy for the provision of valuableprecursors 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 structuraldeterminants responsible for the unique substrate acceptance.

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