A Nicotinamide Mononucleotide (NMN+)-Dependent Redox Cofactor Cycling System Enables Aldehyde Accumulation in Escherichia coli

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 the 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 (98% and 83% product purity in crude lysate- and whole cell-based biotransformation, respectively). We envision the system's universal application to lower the noise in biomanufacturing by silencing the host's metabolic background.