Jacqueline V Shanks
- Manley Hoppe Professor
- Microbial Metabolic Engineering Thrust Leader at NSF Engineering Research Center for Biorenewable Chemicals (CBiRC)
Main Office3031 Sweeney
Ames, IA 50011-2230
Other Office(s)4136 Biorenewables Research Laboratory
Ames, IA 50011
Ph.D. Chemical Engineering, California Institute of Technology, 1989
B.S. Chemical Engineering, Iowa State University, 1983
My current research interests are in the areas of plant and microbial metabolic engineering, particularly in the analytical tools for measuring fluxes and concentrations in metabolic pathways. All projects in my laboratory are in collaboration with plant scientists and biological engineers in a portfolio of metabolic engineering applications: overproduction of valuable plant natural products in hairy roots, synthesis of hydrocarbons in plants and algae, protein and oil production in soybean embryos, and production of biorenewable chemicals from E. coli and S. cerevisiae. My laboratory focuses on the metabolic characterization of the biological system in the ME application and uses several techniques to analyze metabolites, nutrients and fluxes. These include 13C NMR and MS techniques to monitor primary carbon metabolism, HPLC and LC/MSn to measure secondary metabolites.
Metabolic Engineering for Biorenewable Chemicals
Our team of interdisciplinary researchers from CBiRC is designing microbes that can overproduce biorenewable chemicals. A key challenge for the commercial production of biorenewable chemicals is to shorten the metabolic engineering design cycle time for the development of high yielding microbial biocatalysts. Metabolic flux analysis is a key component of this design process. An example of an ongoing collaborative project involves the creation of an integrated flux platform technology. An integrated flux platform technology uses comprehensive experimental flux analysis to mathematically constrain an in silico metabolic model of the microbe, and then computationally predicts the complete set of genetic modifications leading to the overproduction of the target chemical. The genetic interventions are prioritized computationally based on their impact on product yield and ordered in a logic chain. Our ultimate goal is to develop robust integrated flux platform tools that will, in turn, accelerate the commercialization of microbial-based technologies for the efficient production of biorenewable chemicals.
The powerful anticancer agents vinblastine and vincristine are obtained commercially from the intact plants of the periwinkle Catharanthus roseus. The low yield of these valuable indole alkaloids in plants has been the major motivation to produce them by cell and tissue cultures. We are interested in the metabolic engineering of the terpenoid indole alkaloid pathways for the overproduction of valuable alkaloids transgenic C. roseus "hairy root" cultures. Flux of carbon into the alkaloid pathways, diversion of flux at intermediate branches, and lack of final conversion at the end of a specific branch all appear to affect alkaloid production. Precise genetic modification of the pathways and subsequent metabolic analysis of fluxes are enabling the identification of bottlenecks in the "working model" of the pathways. By identifying points of flux limitation, pathway steps then can be pursued for genetic modification in a reiterative process, or if the genes have not been cloned, further studies can be targeted to obtain the unknown information.
Metabolic Flux Maps in Plants
Metabolic flux analysis quantifies the rate of carbon flow for each metabolic reaction in a biochemical pathway model. The approach requires formulation of balanced equations around each metabolite in the network. These metabolite balances are complemented with extracellular measurements of substrate consumption, secretion of metabolites, biomass composition and intracellular measurements such as 13C labeling data detected using nuclear
magnetic resonance (NMR) spectroscopy or mass spectroscopy (MS). Application of 13C labeling-based metabolic flux analysis towards understanding plant physiology has been limited due to the mathematical burden associated with solving a complex model that accounts for comprehensive and rigorous analysis of the NMR data in addition to cellular compartmentation. We have developed a comprehensive generic mathematical tool (NMR2Flux) for metabolic flux analysis that provides network topology information and quantitatively determine fluxes in different cellular compartments. We have applied the metabolic flux map tool in a variety of systems, including soybean embryos, maize cell suspensions, and C. roseus hairy roots.
Honors and Awards
AIChE Food, Pharmaceutical and Bioengineering Division, Area 15c Plenary Award, 2010
Manley R. Hoppe Professor, 2009
Technology Association of Iowa - Research Innovation and Leadership Award, 2008
ISU Foundation Award for Outstanding Achievement in Research, 2005
Van Lanen Award, BIOT Division, ACS, 2004
Fellow, American Institute of Medical & Biological Engineering, 2000
Professional Progress in Engineering Award, ISU, 1994
NSF Young Investigator Award, 1992-1997
Herschel Rich Invention Award, 1992
American Chemical Society
American Institute of Chemical Engineers
American Institute of Medical & Biological Engineering (AIMBE)
Omega Chi Epsilon
Society for In Vitro Biology
Society of Women Engineers
Tau Beta Pi
DOE, The Office of Biological and Environmental Research (BER) Advisory Committee (BERAC), 2011-present
Editorial Advisory Board, Metabolic Engineering, 2011-present
Editorial Advisory Board, Current Opinion in Biotechnology, 2010-present
Editorial Advisory Board, Biotechnology Progress, 2000-present
Chair-Elect, Chair, Past-Chair Biotechnology Division of ACS, 2000-2002
Newsletter Editor, Biotechnology Division of ACS, 1998-2000
National Research Council, Committee on Biobased Industrial Products, 1994-1999
- Jong Moon Yoon, Le Zhao, Jacqueline V. Shanks. "Metabolic Engineering with Plants for a Sustainable Biobased Economy," Annual Review of Chemical and Biomolecular Engineering, Volume 4, In Press, 2013.
- Le Zhao, Guy W. Sander, Jacqueline V. Shanks. "Perspectives of the Metabolic Engineering of Terpenoid Indole Alkaloids in Catharanthus roseus Hairy Roots," Advances in Biochemical Engineering/Biotechnology, In Press, 2013.
- Sridhar Ranganathan, Ting Wei Tee, Anupam Chowdhury, Ali R. Zomorrodi, Jong Moon Yoon, Yanfen Fu, Jacqueline V. Shanks, and Costas D. Maranas. "An Integrated Computational and Experimental Study for Overproducing Fatty Acids in Escherichia coli.," Metabolic Engineering, 14, 687-704 (2012). http://dx.doi.org/10.1016/j.ymben.2012.08.008
- Brown M., Shanks J. V. "Linear Hydrocarbon Producing Pathways in Plants, Algae and Microbes," pp 1-12 In: Sustainable Bioenergy and Bioproducts, Gopalakrishnan, K., van Leeuwen J. H., Brown R. L., Eds., Springer-Verlag, 2012. http://dx.doi.org/10.1007/978-1-4471-2324-8
- Choudhary, M. K., Yoon, J. M., Gonzalez, R., and J. V. Shanks. "Re-examination of metabolic fluxes in Escherichia coli during anaerobic fermentation of glucose using 13C labeling experiments and 2-dimensional nuclear magnetic resonance (NMR) spectroscopy," Biotechnology and Bioprocess Engineering 16, 419-437 (2011). http://dx.doi.org/10.1007/s12257-010-0449-5
- Peebles, C. A. M., Sander, G. W., Hughes, E. H., Peacock, R., J.V. Shanks, and K.-Y. San. "The Expression of 1-deoxy-D-xylulose Synthase and Geraniol 10-hydroxylase or Anthranilate Synthase Increases Terpenoid Indole Alkaloid Accumulation in Catharanthus roseus Hairy Roots," Metabolic Engineering, 13 , 234-240 (2011). http://dx.doi.org/10.1016/j.ymben.2010.11.005
- Murarka, A., Clomburg, J. M., Moran, S., Shanks, J. V. and R. Gonzalez. Metabolic Analysis of Wild-Type Escherichia coli and a Pyruvate Dehydrogenase Complex (PDHC)-deficient derivative reveals the Role of PDHC in the Fermentative Metabolism of Glucose, J. Biological Chemistry, 285, 31548-31558 (2010). http://dx.doi.org/10.1074/jbc.M110.121095
- Peebles, C. A. M., E. H. Hughes, J. V. Shanks, and K.-Y. San. "Transcriptional response of the terpenoid indole alkaloid pathway to the overexpression of ORCA3 along with jasmonic acid elicitation of Catharanthus roseus hairy roots over time," Metab. Eng., 11, 76-86 (2009).
- Iyer, V. V., Sriram, G., Fulton, D. B., Zhou, R., Westgate, M. E., and Shanks, J. V. "Metabolic Flux Maps Comparing the Effect of Temperature on Protein and Oil Biosynthesis in Developing Soybean Cotyledons," Plant Cell and Environment, 31 (4), 506-517 (2008).
- Sriram, G., Fulton, D. B., Iyer, V. V., Peterson, J. M., Zhou, R., Westgate, M. E., Spalding, M. H., and Shanks, J. V. "Quantification of Compartmented Metabolic Fluxes in Developing Soybean (Glycine max) Embryos by Employing Biosynthetically Directed Fractional 13C Labeling, 2-D [13C, 1H] NMR and Comprehensive Isotopomer Balancing," Plant Physiol., 136, 3043-3057 (2004). http://dx.doi.org/10.1104/pp.104.050625