Single-enzyme redox-neutral oxidation of alcohols to carboxylic acids using alcohol dehydrogenases

TL;DR

Scientists found a way to use enzymes to efficiently and cleanly convert alcohols into carboxylic acids using acetone.

Contribution

Discovery of alcohol dehydrogenases capable of single-enzyme oxidation of alcohols to carboxylic acids with acetone as a redox partner.

Findings

Pp-ADH and Aa-ADH enzymes efficiently oxidize alcohols to carboxylic acids.

The method works on 27 diverse alcohols with minimal purification.

In silico studies explain enzyme activity based on structural features.

Abstract

Oxidation of primary alcohols to carboxylic acids is a fundamental reaction in organic chemistry, traditionally dependent on toxic oxidants and often limited by poor selectivity. In this study, we demonstrate the multifunctional capability of some alcohol dehydrogenases (ADHs) to catalyze both alcohol and aldehyde oxidation while regenerating their NAD+ cofactor through concomitant reduction of acetone. Screening of a panel of ADHs revealed that the enzymes from Paracoccus pantotrophus (Pp-ADH) and Aromatoleum aromaticum (Aa-ADH) have strong overoxidation activity to carboxylic acids. The biocatalytic method was assessed for the efficient oxidation of a panel of 27 structurally diverse primary alcohols into carboxylic acids using a single enzyme, with minimal workup and without the need for further purification. The biotransformation was also scaled up using cell-free extracts, while maintaining high yields. In silico studies provided insights into substrate tolerance, highlighting the structural features that govern enzyme activity. This biocatalytic method provides a scalable, selective, and environmentally friendly alternative to conventional oxidation strategies for primary alcohols to carboxylic acids.

This work uncovers alcohol dehydrogenases that enable green, efficient, and selective single-enzyme oxidation of alcohols to carboxylic acids using acetone.

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