Taking Control of Metabolism in Microbial Cell Factories by Applying Noncanonical Redox Cofactors

We have successfully increased the intracellular concentration of NMN to levels sufficient for the activity of NMN-dependent dehydrogenases. In addition, we engineered the cofactor specificity of two key dehydrogenases by reducing their activity with NAD and enhancing their activity with NMN. While these modifications represent important progress, further optimization is required. To this end, we are developing enzyme libraries and constructing rapidly evolving auxotrophic strains to improve enzyme performance. Furthermore, we have generated strains that do not rely on NMN-dependent reactions for growth. We are currently investigating genetic mechanisms that allow regulation between growth and production modes.