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Eric Shiue

Graduate Student

Department of Chemical Engineering
Massachusetts Institute of Technology
Room: E18-522
77 Massachusetts Ave.
Cambridge, MA 02139 USA

Phone: (617) 258-8037
E-mail: ecshiue@mit.edu

Curriculum Vitae

Education

M.S. Chemical Engineering Practice
Massachusetts Institute of Technology (2011)

B.S. Chemical Engineering
University of California, Berkeley (2008)

Research Description

Strategies for the Improvement of D-Glucaric Acid Production in E. coli

D-glucaric acid is a naturally occurring compound which has been explored for a myriad of potential uses, including biopolymer production and cancer treatment. Several additional uses for D-glucaric acid were identified in 2004, when the U.S. Department of Energy named the compound as a “top value-added chemical from biomass” (Werpy and Petersen, 2004). In the Prather Lab, we have constructed a biosynthetic route to produce D-glucaric acid from glucose in E. coli consisting of three heterologous enzymes (Figure, below), yielding D-glucaric acid titers of 1.17 g/L from a 10 g/L glucose feed (Moon et al., 2009). Analysis of the pathway revealed the second heterologous enzyme in this pathway, myo-inositol oxygenase (MIOX), which catalyzes the conversion of myo-inositol to D-glucuronic acid, to be limiting. Soluble expression of MIOX is also much lower than that of the other two heterologous enzymes. In addition, it was observed that the presence of myo-inositol, the substrate for MIOX, to the culture medium resulted in significantly higher MIOX activity.

My research focuses on the development and application of strategies towards the improvement D-glucaric acid production in E. coli. These strategies may be classified broadly into two groups:

  1. Metabolic Engineering

    The field of metabolic engineering focuses on improving the titers, productivity, and/or selectivity of a product of interest via control of cellular metabolism and heterologous pathway flux. A wide variety of strategies are employed to maximize flux through a desired pathway while minimizing the burden imposed by expression of heterologous genes. Such strategies include deletion of off-pathway reactions which siphon flux away from the desired product, overexpression of pathway genes, protein engineering for increased activity, and removal of regulatory mechanisms which may limit pathway flux. Given that MIOX

  2. Synthetic Biology

References

Moon, T.S., Yoon, S.H., Lanza, A.M., Roy-Mayhew, J.D., Prather, K.L.J. “Production of glucaric acid from a synthetic pathway in recombinant Escherichia coli.”  Applied and Environmental Microbiology 75:589-595. (2009) doi: 10.1128/aem.00973-08

Moon, T.S., Dueber, J.E., Shiue, E., and Prather, K.L.J. “Use of modular, synthetic scaffolds for improved production of glucaric acid in engineering E. coli.” Metabolic Engineering 12(3);289-305. (2010) doi: 10.1016/j.ymben.2010.01.003

Shiue, E. and Prather, K.L.J. “Synthetic biology devices as tools for metabolic engineering.”  Biochemical Engineering Journal. 65:82-59. (2012)
doi: 10.1016/j.bej.2012.04.006

Werpy, T. and Petersen, G. “Top Value Added Chemicals from Biomass, Volume I.” (2004) http://www1.eere.energy.gov/biomass/pdfs/35523.pdf

Publications

Shiue, E. and Prather, K.L.J. “Improving D-glucaric acid production from myo-inositol in E. coli by increasing MIOX stability and myo-insotiol transport.”  Metabolic Engineering. 22:22-31 (2014).
doi:10.1016/j.ymben.2013.12.002

Shiue, E. and Prather, K.L.J. “Synthetic biology devices as tools for metabolic engineering.”  Biochemical Engineering Journal. 65:82-89. (2012)
doi: 10.1016/j.bej.2012.04.006

Moon, T.S., Dueber, J.E., Shiue, E., and Prather, K.L.J. “Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli.”  Metabolic Engineering. 12(3):298-305. (2010) doi: 10.1016/j.ymben.2010.01.003