National Science Foundation     |     Directorate for Engineering  (ENG)
Division of Chemical, Bioengineering, Environmental, & Transport Systems  (CBET)
CBET Research Highlights 
Notable Accomplishments from CBET Awards
7644 - Part A - Using Bacteria to Produce Sustainable Fuels and Chemicals
Nathan Price  -  University of Illinois at Urbana-Champaign

Outcome or Accomplishment:  Researchers at the Institute for Systems Biology in Seattle, Washington have developed a model to simulate the metabolism of a butanol-producing bacteria (a biofuel and important chemical) in order to predict the flow of nutrients into and by-products out of the bacteria cells under different conditions.  The predictions will be used to help genetically engineer the bacteria to produce more butanol, an important next-generation biofuel as well as an important feedstock chemical.

Nathan Price Image Image 1     Figure 1.  Overview of butanol production process.
Image Credit:  Nathan D. Price, Institute for Systems Biology, Seattle, WA

Impact:  Modeling the metabolism of butanol-producing bacteria will help speed up the design of a new bacterial strain capable of producing elevated levels of butanol.  Producing butanol biologically provides a sustainable alternative for production of this widely used chemical and potential biofuel and can help reduce dependence on foreign oil.

Explanation/background:  Various microbes have been studied for their ability to produce useful fuels and chemicals from biomass.  Most commonly, researchers have worked to improve ethanol production in microbes in hopes that ethanol could be used as a transportation fuel and reduce our dependence on fossil fuels.  More recently, researchers have turned their attention towards butanol for its improved properties as an alternative fuel and have grown to appreciate its additional value as an important chemical.  Butanol-producing bacteria have been studied in the past, but as of yet the biological butanol production process is not economical (Figure 1).

CBET Research Highlight - Part B - Engineering Technical Information

7644 - Using Bacteria to Produce Sustainable Fuels and Chemicals  

Nathan Price  -  University of Illinois at Urbana-Champaign

Background:  Butanol is a potential fuel additive or replacement and an important chemical used to make products ranging from paints to pharmaceuticals.  Traditionally, butanol is made as a byproduct of the petroleum industry.  With the recent drive to implement sustainable manufacturing practices and reduce United States dependence on foreign oil, producing promising chemicals and fuels such as butanol in microbial fermentations has become an exciting area of research.  To improve the economic viability of producing desired chemicals biologically, most organisms need to be carefully studied and genetically engineered to produce higher levels of the target chemical.  Modeling the metabolism of the chosen fermentation organism enables a whole-cell interrogation and rational (i.e., logically choosing modifications) engineering of metabolism not possible through standard experiments (Figure 1).  Numerous successes have been demonstrated for using these models to guide rational engineering in well-studied microorganisms such as Escherichia coli and Saccharomyces cerevisiae (yeast).

In NSF-supported research, Nathan D. Price and his research group at both the University of Illinois in Urbana, Illinois and the Institute for Systems Biology in Seattle, Washington have built a model to represent all known chemical transformations occurring in the metabolism of the butanol-producing bacteria Clostridium beijerinckiiC. beijerinckii is an attractive organism for biological butanol production because it (i) naturally produces the highest recorded butanol concentrations as a byproduct of fermentation; and (ii) can utilize the major sugar types found in cellulosic (e.g., switchgrass, corn stover) biomass.  Past research has aimed to improve butanol production in C. beijerinckii by performing experiments to better understand its metabolic behavior.  In the present work, the Price group is using computer simulations to understand C. beijerinckii metabolism on a more holistic level and to predict genetic modifications that can be tested experimentally.

Results:  Researchers in the Price group built the first genome-scale metabolic model (named iCM925) for C. beijerinckii, containing 926 genes, 939 reactions, and 881 metabolites.  The iCM925 model enables computer simulation of expected fermentation profiles and thus allows researchers to predict how much butanol (and other known products) will be made under various environmental conditions.  To evaluate predictive accuracy of the model, its ability to reproduce experimentally observed substrate uptake and product production rates was examined.  The model was able to simulate production of experimentally observed compounds (acetone, butanol, ethanol, acetic acid, butyric acid) from glucose.  The production of hydrogen was found to have the largest effect on butanol formation-a relationship that has been experimentally observed as well.  Currently, researchers from the Price group at the Institute for Systems Biology are working to further refine the metabolic model as well as to predict which genes can be removed to increase the amount of butanol produced by C. beijerinckii.
As part of the model building process, the Price group is working to develop methods and software to help reduce the time investment associated with building metabolic models such as the one described herein.  It is more challenging to build models for organisms that do not have extensive experimental data available, such as C. beijerinckii.  As a result, the ability to overcome this limitation is integral to capitalizing on the utility of computer simulated metabolic behavior.  While building their C. beijerinckii model the Price group developed a semi-automated procedure for incorporating genetic information from multiple online databases and assessing the final contribution of each database towards the final simulations.  Additionally, the Price group incorporated existing methods and worked to develop new methods for quickly improving the completeness and predictability of whole-cell metabolic models.

Scientific Uniqueness:  The NSF-funded research is unique because it uses advanced computer models to investigate and advance the long-studied challenge of microbial butanol production by C. beijerinckii.  In addition, the Price group has worked to develop novel methods for utilizing and rapidly developing whole-cell metabolic and regulatory models.  As part of their research, the Price group has also been dedicated to education.  At the University of Illinois, Nathan D. Price developed a course for undergraduate and graduate students to study the employed modeling methods in addition to mentoring numerous undergraduate and graduate students.  Dr. Price also advised the undergraduate University of Illinois software tools team for multiple years in the International Genetically Engineered Machines (IGEM) competition, which won 1st place for best software at the 2009 Jamboree at MIT.  Now at the Institute for Systems Biology, the Price group will continue its dedication to student mentoring and education in the field of Computational and Systems Biology, as is also becoming involved in K-12 outreach activities at ISB.

CBET Strategic Outcome Goals include:
- 1Discovery:  This highlight addresses research that will advance the frontiers of knowledge because it aims to contribute to solving the fundamental challenge of sustainably producing fuels and chemicals and reducing the United States dependence on foreign oil.  If achieved, economical production of biologically-based fuels and chemicals will have an enormous impact on the fundamental approach to science and engineering, and will establish the United States as a global leader in these fields.
- 2Learning:  This highlight addresses research that helps cultivate a broadly inclusive science and engineering workforce by mentoring three graduate students and six undergraduate students in how to conduct exemplary scientific research and contribute to the fields of Computational and Systems Biology.  Additionally, the Price group works to expand the scientific literacy of citizens by offering educational opportunities that survey the field of Computational and Systems Biology.
- 3Research Infrastructure:  This highlight addresses research that helps build the nation's research capability by developing novel computational modeling methods to better understand and improve the metabolic capabilities and industrial potential of microbes.

Transformative Research:  This highlight represents potentially transformative research because it describes a project that aims to demonstrate the success of approaching genetic engineering of important microbes from a computational modeling viewpoint.  Additionally, the success of this research would offer a sustainable and domestic method for producing butanol, and important chemical and alternative transportation fuel.

Intellectual Merit:  The activity described herein has intellectual merit in that it aims to expand open existing metabolic modeling methods and develop novel methods in order to continue to push the frontiers of science.  It combines systems biology models to guide metabolic engineering modifications.  It also forms a basis for building automated approaches to the rapid modeling and reengineering of biomolecular networks in microorganisms.

The Broader Impacts of this research include:
- 1Benefits to society:  The research described herein may benefit society in that it aims to achieve sustainable production of an important chemical and potential biofuel, an outcome that would help reduce the environmental impact of manufacturing processes and United States dependence on foreign oil.
- 2Broadening participation of underrepresented groups:  The research described herein has offered opportunities, mentoring and education to three female graduate students, two female undergraduate students, and two undergraduate students of an underrepresented ethnicity.  The Price group is dedicated to offering positions to a diverse body of interested students.
- 3Advancing discovery and understanding while promoting teaching, training, and learning:  The research described herein has included mentoring of three graduate students and over 20 undergraduate students and thus illustrates strong dedication to teaching, training and learning.  In addition, as part of the NSF-funded research, Nathan D. Price developed and taught a course on Systems Biology and Metabolic Engineering while at the University of Illinois in Urbana, IL.  Dr. Price also advised the undergraduate University of Illinois software tools team for multiple years in the International Genetically Engineered Machines (IGEM) competition, which won 1st place for best software at the 2009 Jamboree at MIT.
- 4Enhancing the infrastructure for research and education:  This funding has led to the development of a course on systems biology at the University of Illinois, which now continues to be taught, despite Dr. Price's move.  The techniques and software developed in the course of building the computational model for C. beijerinckii are being expanded into automated methods that can be very broadly applied.
- 5Results disseminated broadly to enhance scientific and technological understanding:  Research supported by the NSF under this funding has been published in a number of scientific journals for broad dissemination of the findings, including in the Proceedings of the National Academy of Sciences USA, Physical Review Letters, and BMC Systems Biology, a peer reviewed and open access scientific journal.  Going forward, future advances in the project will also be published in peer reviewed journals.  Additionally, the research has been shared in oral presentations at many scientific conferences around the country and the world.  The model itself is also made available for download and can be accessed and used by anyone who is interested in it.

Program Director:
Ram Gupta
CBET Program Director - Energy for Sustainability
NSF Award Number:   0846964
Award Title:   CAREER: Systems Biology and Engineering of Clostridium beijerinckii for Enhancing Butanol Production
Principal Investigator:   Nathan Price
Institution Name:   University of Illinois at Urbana-Champaign
Program Element Code:   7644
CBET Research Highlight:   Fiscal Year 2012
Approved by CBET on:   26 March 2012

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This Award Achievement was Updated on 17 April 2012.