Aldehyde Production in Crude Lysate- and Whole Cell-Based Biotransformation Using a Noncanonical Redox Cofactor System

It is challenging to biosynthesize industrially important aldehydes, which are readily consumed by the numerous alcohol dehydrogenases (ADHs) in cells. In this work, we demonstrate that a nicotinamide mononucleotide (NMN+)-dependent redox cofactor cycling system enables aldehyde accumulation in Escherichia coli crude lysates and whole cells. By specifically delivering reducing power to a recombinant enoate reductase, but not to endogenous ADHs, we convert citral to citronellal with minimal byproduct formation (97–100% and 83% product purity in crude lysate- and whole cell-based biotransformation, respectively). We envision the system’s universal application to lowering the noise in biomanufacturing by silencing the host’s metabolic background.