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T. J. Kappock

Lab Members

Area of Expertise: Resistance strategies in acetic acid bacteria; enzyme mechanism; purine biosynthesis

Biochemistry of acetic acid bacteria (AAB). Bacteria cope with life in harsh environments using specific stress responses and chemical alterations of cell components. The naturally acid-resistant AAB Acetobacter aceti has the ability to survive in molar concentrations of acetic acid at low pH. Most AAB are benign plant-associated organisms. Some strains produce huge amounts of acetic acid by oxidizing ethanol and have been used for millennia to make vinegar. These conditions poison other microbes, nearly all of which (unlike A. aceti) are unable to tolerate an acidic cytoplasm. We use this food-grade organism to explore bacterial acid survival strategies, which are among the most complicated stress responses deployed by microbes, including many pathogenic organisms. Our interests are centered on the adaptation of enzyme function and metabolism to acidic conditions. X-ray crystallographic studies of A. aceti proteins have revealed distinctive architectural features that are correlated with increased acid stability of pure proteins. 

Enzyme mechanism. Enzymes are the gold standard for synthetic chemistry. We are particularly interested in those that form carbon-carbon bonds, among them the purine biosynthesis enzyme PurE and the citric acid cycle enzyme citrate synthase. An example of this remarkable chemistry is the carbon dioxide migration performed by PurE (illustrated above for the microbial form of PurE). Structural, mutagenesis, and pre-steady state kinetics methods are enlisted to understand how these enzymes do their jobs. We typically use enzymes from A. aceti in these studies because they are durable and cooperative.

Awards & Honors

(1989) American Institute of Chemists Award. Northwestern University.

(1995) Predoctoral Fellowship. Howard Hughes Medical Institute.

(1996) Wolfgang Prize for Outstanding Academic Work in Chemistry. Yale University.

(2009) NSF CAREER Award. National Science Foundation.

(2014) Program Chair, 35th Midwest Enzyme Chemistry Conference. Midwest Enzyme Chemistry Conference.

Selected Publications

Lamb, A., Kappock, T., & Silvaggi, N. (2015). You are lost without a map: Navigating the sea of protein structures. Biochim. Biophys. Acta, 1854, 258-268. Retrieved from

Hung, J., Mill, C., Clifton, S., Margrini, V., Bhide, K., Francois, J., Ransome, A., . . . Kappock, T. (2014). Draft genome sequence of Acetobacter aceti strain 1023, a vinegar factory isolate. Genome Announc, 2, (3):e00550-14. doi:10.1128/genomeA.00550-14. Retrieved from

Sullivan, K., Huma, L., Mullins, E., Johnson, M., & Kappock, T. (2014). Metal stopping reagents facilitate discontinuous activity assays of the de novo purine biosynthesis enzyme PurE. Anal. Biochem, 452, 43-45. Retrieved from

Mullins, E., Sullivan, K., & Kappock, T. (2013). Function and X-Ray crystal structure of Escherichia coli YfdE. PLoS ONE, 8, e67901. doi: 10.1371/journal.pone.0067901.

Mullins, E., & Kappock, T. (2013). Functional analysis of the acetic acid resistance (aar) gene cluster in Acetobacter aceti strain 1023. Acetic Acid Bacteria, s1, e3. Retrieved from

Mullins, E., & Kappock, T. (2012). Crystal structures of Acetobacter aceti succinyl-Coenzyme A (CoA):acetate CoA-transferase reveal specificity determinants and illustrate the mechanism used by class I CoA-transferases. Biochemistry, 42, 8422-8434.

Mullins, E., Starks, C., Francois, J., Sael, L., & Kihara, D. (2012). Formyl-coenzyme A (CoA):oxalate CoA-transferase from the acidophile Acetobacter aceti has a distinctive electrostatic surface and inherent acid stability. Protein Sci, 21, 686-696.

Perez-Jimenez, R., Ingles-Prieto, A., Zhao, Z., Sanchez-Romero, I., Alegre-Cebollada, J., & Kosuri, P. (2011). Single-molecule paleoenzymology probes the chemistry of resurrected enzymes. Nat. Struct. Mol. Biol, 18, 592-596. Retrieved from

Tranchimand, S., Starks, C., Mathews, I., & Hockings, S. (2011). Treponema denticola PurE is a bacterial AIR carboxylase. Biochemistry, 50, 4623-4637.

Kurz, L., Constantine, C., & Jiang, H. (2009). The partial substrate dethiaacetyl-coenzyme A mimics all critical carbon acid reactions in the condensation half-reaction catalyzed by Thermoplasma acidophilum citrate synthase. Biochemistry, 48, 7878-7891.