Tuesday, November 6, 2007 - 4:10 PM
274c

Analysis Of Networks Perturbed By Butanol Toxicity

Mark P. Brynildsen and James C. Liao. Chemical and Biomolecular Engineering, University of California, Los Angeles, 420 Westwood Plaza, 5531 Boelter Hall, Los Angeles, CA 90095

Butanol has received attention recently as a renewable resource fuel alternative due to a number of attractive attributes, such as its comparable energy content to gasoline, compatibility with current infrastructure, and ability to be fermented from a wide variety of carbon sources. However, butanol toxicity is a main concern, with native producing strains (Clostridium acetobutylicum) being unable to grow at concentrations of 1.5% vol/vol (1). The deleterious effects of butanol have mainly been attributed to disruption of the membrane, but recent work suggests that butanol toxicity is much more complex (2,3). To understand butanol toxicity we have applied an approach that integrates transcriptomic, proteomic, metabolic, and phenotypic data to identify networks in Escherichia coli perturbed by butanol toxicity. By the use of DNA microarray, phenotypic experiments, proteomic and metabolic data, and bioinformatics techniques including Network Component Analysis we have characterized the butanol response network 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 butanol production.

1. Vollherbst-Schneck, K., J.A. Sands, and B.S. Montenecourt (1984) Effect of butanol on lipid composition and fluidity of Clostridium acetobutylicum ATCC 824. Appl. Environ. Microbiol. 47:193–194.

2. Tomas, C. A., N.E. Welker, and E.T. Papoutsakis (2003) Overexpression of groESL in Clostridium acetobutylicum results in increased solvent production and tolerance, prolonged metabolism, and large changes in the cell's transcriptional program. Appl. Environ. Microbiol. 69:4951–4965.

3. Borden, J.R., and E.T. Papoutsakis (2007) Dynamics of Genomic-Library Enrichment and Identification of Solvent Tolerance Genes for Clostridium acetobutylicum. Appl. Environ. Microbiol.73:3061-3068.