Pfleger, Brian F.

L. Kizer, D. J. Pitera, B. F. Pfleger, and J. D. Keasling. Functional Genomics for Pathway Optimization: Application to Isoprenoid Production., Appl Environ Microbiol 2008, (Epub ahead of print).
S. K. Lee, H. H. Chou, B. F. Pfleger, J. D. Newman, Y. Yoshikuni, and J. D. Keasling. Directed Evolution of AraC for Improved Compatibility of Arabinose- and Lactose-Inducible Promoters. Applied and Environmental Microbiology. 73(18), 5711-5715, (2007).
Pfleger, B. F.; Lee, J. Y.; Somu, R. V.; Aldrich, C. C.; Hanna, P. C. et al. Characterization and Analysis of Early Enzymes for Petrobactin Biosynthesis in Bacillus anthracis. Biochemistry 2007, 46, 4147-4157.
Pfleger, B. F.; Pitera, D. J.; Newman, J. D.; Martin, V. J.; Keasling, J. D. Microbial sensors for small molecules: development of a mevalonate biosensor. Metab Eng 2007, 9, 30-38.
Lee, J. Y.; Janes, B. K.; Passalacqua, K. D.; Pfleger, B. F.; Bergman, N. H. et al. Biosynthetic Analysis of the Petrobactin Siderophore Pathway from Bacillus anthracis. J Bacteriol 2007, 189, 1698-1710.
Pfleger, B. F.; Pitera, D. J.; Smolke, C. D.; Keasling, J. D. Combinatorial engineering of intergenic regions in operons tunes expression of multiple genes. Nat Biotechnol 2006, 24, 1027-1032.
Pfleger, B. F.; Fawzi, N. J.; Keasling, J. D. Optimization of DsRed production in Escherichia coli: effect of ribosome binding site sequestration on translation efficiency. Biotechnol Bioeng 2005, 92, 553-558.

Selected Awards, Honors and Societies

2006-2007 Great Lakes Regional Center of Excellence Postdoctoral Training Fellowship

Summary

My research interests lie in developing microorganisms capable of producing small molecules of significant social, economic, and scientific value from renewable resources. In the past decades, the field of biotechnology has blossomed to allow the production of valuable proteins including restriction enzymes, polymerases, blood factors, antibodies, and other therapeutic enzymes at industrial scale and cost. Recent work has shifted towards the production of small therapeutic molecules that are difficult to synthesize de novo due to their complexity. The high value ($ per molecule) of these chemicals allows for an economically viable process to be designed using today's technologies. In the coming decades, our economy will need to be based on renewable resources in order to sustain itself. As such, the chemical industry will need to discover renewable sources for its specialty chemicals and materials that are currently derived from fossil fuels. To reach such ends, my research group will develop new tools for engineering biological systems and explore the world of protein engineering in order to develop new biological catalysts for essential chemical reactions. It is my goal to develop a leading laboratory in the field of Synthetic Biology in order to harness the growing database of biological parts for use in developing novel technologies for chemical synthesis.

Synthetic Biology is defined as the design and construction of new biological parts, devices, and systems, and the re-design of existing, natural biological systems for useful purposes. Chemical engineers should be among the leaders in this field. With our training in chemical process design, we are positioned to make great strides in developing practical chemical processes utilizing biological means. In the recent past, work in Synthetic Biology has focused on the development of tools to meet the first part the above definition. Advances in control strategies like riboswitches, which utilize RNA binding of small molecules to regulate gene expression, are providing opportunities for the development of novel biosensors and cell signaling pathways. The increasing size of the catalog of characterized biological parts is providing opportunities to design larger and more complex genetic circuits. Advances in our understanding of gene expression, including the use of intergenic regions to control relative protein expression, are providing the tools necessary to build strains capable of producing valuable chemicals, like the important anti-malarial compound, artemisinin. Production of artemisinin through fermentation has the potential to provide a desperately needed drug at a stable, low cost. If microorganisms can be engineered to produce these complex molecules, then biological production other simple molecules should also be possible.

It is a commonly held belief that the world's fossil fuel reserves will run dry in the not too distant future. While the chief concern with this problem is how the world's energy needs will be met, we should also be concerned about the source of the chemicals and materials that are currently extracted/produced from fossil fuels. The list of fossil fuel-derived products is long and filled with common everyday items. Chief among these are plastics, (polyethylene, polystyrene), solvents, and other organic building blocks. As fossil fuel supplies decrease, recycling and reuse will help reduce supply problems, but will not provide a sustainable solution. Biological production of specialty chemicals and materials may be able to supply the remaining need. Fermentation of biomass into ethanol is already a major focus of research and is becoming increasingly viable economically. The advances in biomass utilization and fermentation yields should be extended beyond ethanol and into production of other low price, high value chemicals. In the short term, engineering a microorganism to produce polymer precursors from sugars will provide a strategic and environmentally friendly alternative to processes that utilize fossil fuels. Down the road, advances in biomass cultivation and processing should further decrease the cost of biological production and provide the renewable source needed for sustainability.

Copyright 2008 The Board of Regents of the University of Wisconsin System
Date last modified: 30-Jul-2008
Content by: pfleger@engr.wisc.edu
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