Metabolic Engineering for Biocatalyst Robustness to Organic Inhibitors

Microbial production of biorenewable fuels and chemicals is often limited by inhibition of the biocatalyst, either by increasing concentrations of the product compound or by contaminant compounds in the biomass‐derived sugars. This inhibition can interfere with economically viable production. Here we discuss typical mechanisms of inhibition and methods for improving biocatalyst robustness. Inhibition often takes the form of inhibition of enzyme activity, depletion of cofactor pools, and membrane damage; methods are discussed for mitigating each of these types of inhibition. Various evolutionary schemes have been developed and implemented on a variety of inhibitory compounds, including butanol, acetic acid, furfural, and ethanol. Reverse engineering of these improved strains can provide insight into new metabolic engineering strategies