Evaluating Potential of Ethanol-Based NADH Regeneration in Supporting Whole-Cell Biocatalysis

Abstract

Many cofactor regeneration systems have been explored for NADH regeneration in support of biocatalytic reactions in whole cells. But, many of these systems suffer from poor cofactor yield and regeneration efficiency. Ethanol is emerging as an important commodity chemical in the world given its increasing production from biological fermentation of biomass. Possibility exists in using a nature inspired ethanol utilization pathway in transforming ethanol to acetyl-CoA through a two-step reaction sequence that yields one NADH at each step. Theoretically more efficient than the state-of-the-art glucose dehydrogenase system, ethanol utilization may be suitable for development as a cofactor regeneration system for biocatalysis and metabolic engineering. This perspective outlines and review prior works on the origins of the pathway, alternative NADH regeneration systems, and different modes (resting or growing cell) in which ethanol utilization pathway could be usefully employed in supporting a biotransformation reaction in whole cells.