Structural and mechanistic insights into activators of alcohol dehydrogenase

Interest in the activation of alcohol dehydrogenases (ADHs) arises from reports that ADH activation can ameliorate alcohol-related disease states. ADH activation was also suggested to play a role in longevity. In addition, ADHs are valuable biocatalysts for the synthesis of fine chemicals where ADH activation could allow for the use of lower amounts of expensive enzymes in biocatalytic processes. In recent years, there has been a surge of interest in the use of peptides and small molecules to activate ADH. Remarkably, over 100 peptides have been shown to activate ADH, mostly derived from food sources. In addition to food-derived peptides, ADH is activated by certain naturally occurring polyphenols, polysaccharides, catechins, quaternary ammonium compounds and in the presence of deep eutectic solvents. Few reviews to date address the broad range of ADH activation studies and examine the gaps in our knowledge of the mechanism of ADH activation. The relationship between different forms of activation is still not understood and, in most cases, the exact interaction sites are not known. This review focuses on the mechanistic aspects of ADH activation and the integration of physiological/therapeutic aspects with biocatalytic/industrial applications. It is hoped that it will contribute to a roadmap for future studies.