The ‘water challenge’: Opportunities and challenges of using oxidoreductases in non-conventional media


*Corresponding author
1. Institute of Technical Biocatalysis, Hamburg University of Technology, Hamburg, Germany
2. Sustainable Momentum, Canary Islands, Spain


Biocatalysis has become a mature technology for many synthetic applications. In this discipline, the use of enzymes in non-aqueous environments (so-called ‘non-conventional’ media) has attracted considerable attention during the last years, as high substrate loadings, volumetric productivities and product titers may be achievable, enabling practical outcomes. The use of hydrolases in non-aqueous media is an established approach already proven at industrial scale. Surprisingly oxidoreductases – which catalyze synthetically interesting reduction-oxidation reactions – have been limitedly applied in low-water-content conditions until very recently. This review focuses on the recent achievements in applying oxidoreductases in non-conventional media namely, use of neat-substrates, organic solvents and deep eutectic solvents, with critical emphasis on the opportunities and current challenges of those strategies.


Oxidoreductases (EC 1) catalyze synthetically useful redox processes, ranging from reduction of C=O, C=C, and other functional groups, to specific oxyfunctionalization reactions such as hydroxylation, epoxidation or Baeyer–Villiger reactions (1-4). Following hydrolases (EC3), redox enzymes have been the most commonly applied biocatalysts in industry especially for the synthesis of active pharmaceutical intermediates (APIs) and fine chemicals, owing to their selectivity advantages (stereo-, chemo-, regio-). However, due to the limited water solubility of non-polar or moderately polar reagents high volumetric productivities are not typically reached which consequently renders the process to be economically feasible. Furthermore, water as a reaction medium may cause several limitations due to the water-induced side reactions, cumbersome downstream processing, enzyme inhibition by substrates/products, water-induced enzyme denaturation, and even microbial contamination risks. In this respect, the use of non-conventional media can overcome these water-related limitations ensuring high product titers and yields and ease of product isolation. However, whils ...