Delaware researchers awarded DOE grant for genomic research

By Bryan Sims | November 17, 2011

The production of advanced biofuels, such as biobutanol, on a commercial scale is one focus within the biorefining industry, but the high conversion rate required coupled with high levels of toxins that cells are exposed to, particularly within a fermentation-based platform, can greatly affect, and oftentimes impede, positive economic return of the operation. To counter this, bioengineering scientists at the University of Delaware are working to create microrganisms that are more resistant to toxic chemicals, such as solvents and carboxylate acids, to withstand the stress response that can inhibit cell growth and cause cell death. The research is funded through a $2.2 million grant from the U.S. DOE.

According to Eleftherios (Terry) Papoutsakis, Eugene du Pont Chairman of Chemical Engineering at UD, the scope of research consists of utilizing an experimental systems-biology approach to support the development of integrated, predictive models of the metabolic and regulatory networks underlying the metabolite stress response in solventogenic clostridia, a common anaerobe used in fermentation-based cultures for conversion of biomass to biofuels.

Papoutsakis has assembled a group of researchers with expertise in genetics and genomics, genomic tools and analysis, bioinformatics, biological model building and genome scale modeling to conduct this research.

According to Papoutsakis, the core of work involves using high-throughput genomic technology to examine the RNA of the clostridia species. The data collected will be used to develop two models for the metabolite stress response, which will enable the team to create a second-generation genome-scale model (GSM), a complex model of the entire metabolism of the cell, map all of the literature data that exists based on 10 years of previous study on the organism as well as the new data the team plans to generate to the genetic information of the GSM in order to better understand the stress-response of Clostridium acetobutylicum that produces butanol and butyrate at the molecular level.

“We use carbon 13 with gas chromatography mass-spectrometry to be able to examine phlaxis and how the metabolism changes under stress,” Papoutsakis explained. “We’re developing much more sophisticated genome scale models to be able to lay over the stress responses and model that such that we can presumably pinpoint what kind of genetic modifications we need to make to be able to engineer a more tolerant organism to the chemicals being produced because they’re all toxic to the cells.”

The ongoing research, according to Papoutsakis, is expected to have a positive long-term affect for participants within the biorefining industry to economically and cost-effectively produce biobased chemicals like butanols and butyrates during their scale-up efforts.

“If you can increase the level of the toxins you get either in batch or fed batch continuous cultures by even 5 or 10 percent that’s going to improve the economics enormously,” he said.

Papoutsakis added that he envisions the work to not be exclusive to Clostridium but it could also be applied to other types of organisms, anaerobes and other platform organisms such as E. coli or yeast cells. In addition to Papoutsakis, the research team includes five UD faculty members and a collaborator at Pennsylvania State University.