Summary

The central research theme for our laboratory is the biosynthesis and degradation of simple and complex carbohydrates both at the construction level, cellular control and physiological function. One of our long-standing research interests involves the biosynthesis and physiological roles of the lipopolysaccharide portion of pathogenic Gram-negative microorganisms, in particular the 3-deoxy-D-manno-oct-2-ulosonic acid (kdo) biosynthetic/attachment branch. These studies involved the expression, biochemical characterization, and structure determination of the individual enzymes in the pathway. Recent investigations involve the careful mapping of the pathway for the assembly of the inner and outer core regions of LPS utilizing a genomic knockout methodology coupled with the isolation, biochemical characterization and structural determination of the individual enzymes involved in the assembly.  The role/function as well as control of multicopies, of several key enzymes in the kdo pathway are being investigated.

 

A second interest involves the biosynthesis of the aromatic amino acids, tyrosine, phenylalanine and tryptophan in bacteria, with our main focus on the differential feedback control of the isozymes of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase as well as their orchestration in cellular functions. Studies on the evolution and structure of these enzymes have provided clues as to control structure/function.

 

In collaboration with Professor Jing Wu, Jiangnan University, Wuxi, China, we are investigating the industrial production of extracellular enzymes in E. coli capable of degradation of plant cellulosic biomass into food and/or fuel sources. As the most abundant biopolymer on earth, cellulose is an attractive source for production of simple carbohydrates.

Awards

  • 2007 Fellow, American Association for the Advancement of Science
  • 2013 Top Five Innovations in the WORLD by The Scientist
  • 2014 Foreign Expert in Science

Selected Publications

  • Wu, Jing, Galina Ya. Sheflyan and Ronald W. Woodard, Biochemical Journal, 390, 583-590 (2005) “Bacillus subtilis 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase revisited: resolution of two long-standing enigmas.”

  • Meredith, Timothy C., Parag Aggarwal, Uwe Mamat, Buko Lindner, and Ronald W. Woodard, ACS-Chemical Biology, 1, 33-42 (2006) “Redefining the Requisite Lipopolysaccharide Structure in Escherichia coli.”

  • Mamat, Uwe, Timothy C. Meredith, Parag Aggarwal, Annika Kühl, Paul Kirchhoff, Buko Lindner, Anna Hanuszkiewicz, Jin Sun, Otto Holst, and Ronald W. Woodard, Mol Microbiol., 67(3), 633-648 (2008) “Single Amino Acid Substitutions in either YhjD or MsbA confer Viability to 3-deoxy-D-manno-oct-2-ulosonic acid-depleted Escherichia coli.”

  • Biswas T, Li Yi, Parag Aggarwal, Jing Wu, J. R. Rubin, Jenna A. Stuckey, Ronald W.Woodard, Oleg V. Tsodikov, Journal of Biological Chemistry, 284, 30594-603 (2009) “The Tail of KdsC: conformational changes control the activity of a Haloacid Dehalogenase Superfamily Phosphatase.”

  • Schmidt, Helgo, Guido Hansen, Sonia Singh, Anna Hanuszkiewicz, Buko Lindnerd, Koichi Fukasee, Ronald W. Woodard, Otto Holst, Rolf Hilgenfeld, Uwe Mamat and Jeroen R. Mestersa, Proceeding of National Academy Sciences USA, 109, 6253-6258 (2012) “Structural and mechanistic analysis of the membrane-embedded glycosyltransferase WaaA required for Aquifex aeolicus lipopolysaccharide synthesis.”