Matthew D. Blankschien, Ph.D.

Peter and Ruth Nicholas Postdoctoral Fellow

Education

Ph.D., Molecular Genetics, Baylor College of Medicine, June 2009
B.S., Chemistry, University of Wisconsin-Green Bay, May 2001

Project Description

Glycerol has become an ideal feedstock for the microbial synthesis of biochemicals due to its high degree of reduction, abundance, and plummeting prices. The Gonzalez Laboratory has previously delineated the pathways for the fermentative use of glycerol by Escherichia coli in minimal salts media under microaerobic conditions. With my project, I have capitalized on such results to engineer E. coli for the production of value-added succinic acid (succinate, C4H6O4) from glycerol that could become a central platform chemical to produce a wide spectrum of products such as: pharmaceuticals, food additives, biodegradable plastics, paints, green solvents, deicers, and fuel additives.

Through rational design, succinate production was greatly elevated by 1) blocking pathways for the competing production of lactate (ΔldhA), ethanol (ΔadhE), and acetate (Δpta), and 2) expressing Lactococcus lactis pyruvate carboxylase in E. coli to sequester CO2 and drive the generation of succinate from pyruvate, circumventing low phosphoenolpyruvate levels. This metabolic engineering strategy coupled cell growth to succinate production because the creation of succinate remained as the primary route of NAD+ regeneration Our succinate biocatalysts demonstrated a maximum productivity of 25.8 mg/L/h (specific productivity 96.7 mg/h/g) and at a yield of 54% (69% g/g) of theoretical maximum.

While this is the first description of metabolically engineering E. coli to produce succinate from glycerol, performances are on par to those achieved in the equivalent synthesis of organic acids from sugars using recombinant E. coli strains.

Publications

Matthew Blankschien, James M. Clomburg, Ramon Gonzalez. Metabolic engineering of Escherichia coli for the production of succinate from glycerol. Metabolic Engineering 2010, Sep; 12(5): 409-19. Epub 2010 Jun 22.
Ashley K. Tehranchi, Matthew D. Blankschien, Yan Zhang, Anjana Srivatsan, Jia Peng, Christophe Herman, and Jue D. Wang. The transcription factor DksA prevents conflicts between DNA replication and transcription transcription machinery. Cell 2010, May 14; 141(4): 595-605.
Natalie C. Fonville, Matthew D. Blankschien, Daniel B. Magner, and Susan M. Rosenberg. RecQ-dependent death-by-recombination in cells lacking RecG and UvrD. DNA Repair 2010, April 4; 9(4): 403-413. Epub 2010 Feb 4.
Matthew D. Blankschien, Jeong Hyun, Elicia Grace, Jennifer Halliday, Wilma Ross, Richard L. Gourse, and Christophe Herman. Novel mutations of dksA that enable modulation of RNAP in the absence of ppGpp. EMBO Journal 2009, Jun 17;28(12):1720-31. Epub 2009 May 7.
Alasdair J.E. Gordon, Jennifer A. Halliday, Matthew D. Blankschien, Philip A. Burns, Fumio Yatagai, and Christophe Herman. Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network. PLoS Biology 2009, Feb 24; 7 (2): e44.
Matthew D. Blankschien, Katarzyna Potrykus, Elicia Grace, Abha Choudhary, Daniel Vinella, Michael Cashel, and Christophe Herman. TraR, a homolog of a secondary channel interactor, modulates transcription. PLoS Genetics 2009, Jan 16; 5 (1): e1000345
Matthew D. Blankschien*, Daniel B. Magner*, Jennifer A. Lee, Jeanine M. Pennington, James R. Lupski and Susan M. Rosenberg. RecQ promotes toxic recombination in cells lacking recombination intermediate-removal proteins. Mol Cell. 2007, April 27; 26 (2): 273-286 * These authors contributed equally to this work.
Gen Nonaka, Matthew D. Blankschien, Christophe Herman, Carol A. Gross, and Virgil A. Rhodius. Regulon and promoter analysis of the E. coli heat shock factor, Sigma 32, reveals a multifaceted cellular response to heat stress. Genes Dev. 2006, Jul 1; 20 (13): 1776-17892.2

Awards

Peter and Ruth Nicholas Postdoctoral Fellowship, 2011

BCM Molecular and Human Genetics Best Student Paper, 2007

Fellowship to Molecular Genetics of Bacteria and Phage Meeting, Madison, WI, 2007

Graduated Magna Cum Laude, 2001

Robert E. Lee & Associates Scholarship in Chemistry, 2000

UWGB Faculty Science and Mathematics Scholarship, 2000

Nancy A. Sell Memorial Scholarship, 1999

Mason Scholarship, 1996

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