Jason J. Reddick
Characterization of Metabolic Pathways in Bacillus subtilis in the Post-Genomic Era
After over a century of combined accomplishments in the fields of biology, biochemistry, molecular biology, and genomics, we still do not have a complete understanding of the chemical processes necessary for Life. New technologies and the public availability of genomic data have enhanced the practice of these biomolecular and biological fields, but the pace that new genome sequences are completed now far exceeds our true ability to comprehensively and efficiently cope with this data. Ultimately, each gene needs characterized one-by-one in order to achieve the high level of accuracy needed by database annotations. It is not uncommon that experimental data contradict the statistical bioinformatics used to annotate a genome; indeed this type of experimental data is the only means by which original annotations can be refined. Bacillus subtilis is the model Gram positive bacterium, and is also the model for the study of sporulation, an important example of prokaryotic cell differentiation. Despite the fact that B. subtilis was one of the first organisms whose genome was fully sequenced, only about 40% of the proteins encoded by this comparatively small genome have been biochemically characterized in vitro. It is perhaps even more surprising that some major metabolic pathways which likely supply energy and carbon during sporulation remain biochemically unstudied as well. We therefore still do not fully understand the metabolism necessary to complete the process of sporulation. This incomplete understanding is a problem, because it prevents the comprehensive use and study of this relatively well-characterized and useful model organism. A long-term goal of our research is to contribute to the in vitro annotation of the B. subtilis genome, in particular metabolic genes used during sporulation.
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Reddick, J.J.; Antolak , S.A. ; Raner, G.M. "PksS from Bacillus subtilis is a Cytochrome P450 Involved in Bacillaene Metabolism."Biochem. Biophys. Res. Commun. 2007, 358, 363.
Melnick, J.S.; Sprinz, K.I.; Reddick, J.J.; Kinsland, C.; Begley, T.P. “An efficient enzymatic synthesis of thiamin pyrophosphate.” Bioorg. Med. Chem. Lett.2003, 13, 4139.
Reddick, J.J.; Cheng, J.; Roush, W.R. "Michael Reactions of Phenethylthiol with Vinyl Sulfones, Vinyl Sulfonate Esters and Vinyl Sulfonamides Relevant to Vinyl Sulfonyl Cysteine Protease Inhibitors." Org. Lett. 2003, 5, 1967.
Reddick, J.J.; Saha, S.; Lee, J-M.; Melnick, J.S.; Perkins, J.; Begley, T.P. "The Mechanism of Action of Bacimethrin, a Naturally Occurring Thiamin Antimetabolite." Bioorg. Med. Chem. Lett. 2001, 11, 2245.
Reddick, J.J.; Nicewonger, R.; Begley, T.P. "Mechanistic Studies on Thiamin Phosphate Synthase: Evidence for a Dissociative Mechanism." Biochemistry2001, 40, 10095.
Peapus, D.H.; Chiu, H-J.; Campobasso, N.; Reddick, J.J.; Begley, T.P.; Ealick, S.E. "Structural Characterization of the Enzyme-Substrate, Enzyme-Intermediate, and Enzyme-Product Complexes of Thiamin Phosphate Synthase." Biochemistry 2001, 40, 10103.