Structural insights into alcohol dehydrogenases catalyzing asymmetric reductions

Abstract

Alcohol dehydrogenases are a group of oxidoreductases that specifically use NAD(P)⁺ or NAD(P)H as cofactors for electron acceptance or donation and catalyze interconversion between alcohols and corresponding carbonyl compounds. In addition to their physiological roles in metabolizing alcohols and aldehydes or ketones, alcohol dehydrogenases have received considerable attention with respect to their symmetry-breaking traits in catalyzing asymmetric reactions and have Accordingly, they have become widely applied in fine chemical synthesis, particularly in the production of chiral alcohols and hydroxyl compounds that are key elements in the synthesis of active pharmaceutical ingredients (API) employed in the pharmaceutical industry. The application of structural bioinformatics to the study of functional enzymes and recent scientific breakthroughs in modern molecular biotechnology provide us with an effective alternative to gain an understanding of the molecular mechanisms involved in asymmetric bioreactions and in overcoming the limitations of enzyme availability. In this review, we discuss molecular mechanisms underlying alcohol dehydrogenase-mediated asymmetric reactions, based on protein structure–function relationships from domain structure to functional active sites. The molecular principles of the catalytic machinery involving stereochemical recognition and molecular interaction are also addressed. In addition, the diversity of enzymatic functions and properties, for example, enantioselectivity, substrate specificity, cofactor dependence, metal requirement, and stability in terms of organic solvent tolerance and thermostability, are also discussed and based on a comparative analysis of high-resolution 3 D structures of representative alcohol dehydrogenases.

Keywords:

• Alcohol dehydrogenase
• structure
• function
• characteristics
• molecular mechanism
• asymmetric biotransformation

Acknowledgements

We would like to thank Editage (www.editage.cn) for English language editing.

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

Financial support was obtained from the following sources, all of which are gratefully acknowledged: the National Natural Science Foundation of China (NSFC) (21336009, 21676120, 31872891), the Natural Science Foundation of Jiangsu Province (BK20151124), the 111 Project (111–2-06), the High-end Foreign Experts Recruitment Program (GDT20183200136), the Program for Advanced Talents within Six Industries of Jiangsu Province (2015-NY-007), the National Program for Support of Top-notch Young Professionals, the Fundamental Research Funds for the Central Universities (JUSRP51504), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Jiangsu province "Collaborative Innovation Center for Advanced Industrial Fermentation" industry development program, Top-notch Academic Programs Project of Jiangsu Higher Education Institutions, and the National First-Class Discipline Program of Light Industry Technology and Engineering (LITE2018-09).