Abstract

Inhibition of bacterial metabolism hinders production of biorenewable compounds. Transcriptome analysis can be used to identify the mechanism of bacterial inhibition. Randomly selected tolerant strains can be reverse engineered to find key mutations. When the mechanism of inhibition is known it can be rationally alleviated. Efflux pumps and alteration of the cell membrane are increasingly important.

Metabolic Engineering has enabled the production of biorenewable fuels and chemicals from biomass using recombinant bacteria. The economic viability of these processes is often limited by inhibition of the biocatalyst by the metabolic product, such as a carboxylic acid or alcohol, or by contaminant compounds in the biomass-derived sugars, such as acetic acid or furans. Historically, selection-based methods have been used to improve biocatalyst tolerance to these inhibitors. But recently, genome-wide analysis has been used to both identify the mechanism of inhibition and reverse engineer inhibitor-tolerant strains, enabling the rational, predictive manipulation of bacteria in order to increase inhibitor tolerance. Here we review recent work in this area, particularly in relation to carboxylic acids, furfural and butanol.