Identification of networks perturbed by isobutanol and butanol toxicity

Isobutanol and butanol have received attention recently as renewable resource fuel alternatives (1-3). However, toxicity is a main concern for these biofuels, with native butanol producing strains (Clostridium acetobutylicum) being unable to grow at concentrations of 1.5% vol/vol (4). The deleterious effects of alcohols have mainly been attributed to disruption of the membrane, but recent work suggests that toxicity is much more complex (5-7). To understand isobutanol and butanol toxicity we have applied an approach that integrates transcriptomic, metabolic, protein, and phenotypic data to identify networks in Escherichia coli perturbed by isobutanol and/or butanol. By the use of DNA microarray, gene knockouts, phenotypic experiments, protein and metabolic data, and bioinformatics techniques including Network Component Analysis we have characterized the isobutanol and butanol response networks of E. coli. Escherichia coli was chosen as our model organism instead Clostridium strains due to similar growth toxicity (unable to grow at concentrations of 1% vol/vol), the degree to which the transcription, metabolic, and protein-protein interaction networks of E. coli have been identified, and the potential of E. coli to be used as a host strain for biofuel production.