About this Research Topic

Background

Reduction and oxidation involving carbon-oxygen bonds are crucial transformations in organic synthesis. These reactions also occur efficiently and selectively in living organisms catalyzed by enzymes. Among them, Alcohol Dehydrogenases (E. C. 1.1.1) (ADHs) have emerged in the last decades as useful biocatalysts to perform mild oxidation of alcohols, and on the other hand, to afford enantiopure alcohols from ketones. These enzymes catalyze the reduction of aldehydes and ketones at the expenses of cofactor NAD(P)H as hydride source and the reverse reaction using NAD(P)+ as oxidant.

In contrast to non-enzymatic methods, which often require toxic oxidants in stoichiometric amounts or expensive transition metals and harsh conditions, ADHs offer advantages such as activity under mild conditions, biodegradability, and availability from renewable sources. Importantly, ADHs display high selectivity, so that their use may shorten synthetic routes, and remarkable stereoselectivity to compete with chemo-catalysts, thus being very attractive for the synthesis of fine chemicals, especially chiral alcohols.

Despite having proven useful for synthetic purposes, including industrial applications, ADHs are still underexploited among synthetic organic chemists. Drawbacks commonly associated with biocatalysis, such as low catalyst thermostability and tolerance to organic solvents, narrow scope, unflexible enantio preference, and limited availability may be the main reasons for this observation, whether they are real or just assumed. Particularly for ADHs, the need for cofactor regeneration systems to avoid stoichiometric use of expense nicotinamide coenzymes is an additional challenge. Conversely, advances in recombinant DNA technology, bioinformatics, protein engineering, and biocatalyst immobilization in the last decades have provided powerful tools for addressing these issues, so that the current scenario is very favorable for biocatalysis to become a more popular and well-established field within organic synthesis.

Moreover, biocatalysis can offer valuable opportunities in the search for greener processes in the pharmaceutical, fine chemicals, and even bulk chemical industries to meet the urgent demand for sustainability. In this sense, the development of practical methods based on ADHs that can be conveniently employed in chemistry laboratories or facilitate their use by synthetic chemists, such as methods to improve enzyme production and cofactor regeneration, may contribute to paving the way of ADHs from an alternative towards a mainstreams approach in organic synthesis.

The present Research Topic is focused on the application of ADHs in organic synthesis and covers research manuscripts and reviews concerning :
- Practical use of ADHs in the synthesis of ketones and chiral alcohols, including academic and industrial applications
- Strategies for cofactor regeneration in ADH-catalyzed reactions
- Strategies for improving ADHs application in organic synthesis (immobilization, protein
engineering, medium engineering, continuous flow synthesis …)
- Use of ADHs in (chemo)enzymatic cascades
- Methods for producing ADHs for application in organic synthesis
- Investigation of mechanistic aspects of ADH catalysis

Keywords: Alcohol Dehydrogenases, Asymmetric Reduction, Enzymatic Oxidation, Organic Synthesis, Biocatalysis

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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