个人简介

B.Sc., University of Alberta, 1985; Ph.D., University of California, Los Angeles (D.J.Cram, 1990); NSERC Postdoctoral Fellow, Harvard University (J.R.Knowles, 1990-1992)

研究领域

Biological & Medicinal Chemistry; Chemical Synthesis; Organic Chemistry

Our efforts focus on developing a detailed understanding of the mechanisms by which enzymes catalyze biological reactions. Insights obtained from studies on enzyme mechanism can lead to the production of bio-active compounds and to the design of efficient synthetic catalysts. Stereochemical control is a key component in the biosynthesis and metabolism of many biological compounds. As a result, many racemases and epimerases have evolved that catalyze the inversion of configuration about carbon. Most of these enzymes act at centers which are activated by an adjacent carbonyl functionality, and they abstract a relatively acidic proton. Our interests lie in studying enzymes that act on unactivated stereocenters and must employ unique reaction mechanisms. One example is ADP-heptose 6-epimerase that generates a key building block in bacterial lipopolysaccharide biosynthesis. Another area of current interest in the Tanner group are the enzymes responsible for the biosynthesis of the sialic acids in mammals. Sialic acids are found on the surface of mammalian cells and play key roles in mediating cellular recognition events. Studies on both the epimerase and the synthase are currently ongoing in the lab. Sialic Acid Biosynthesis in Mammels A wide range of experimental techniques are used to probe the reaction pathways. The tools of physical organic chemistry, such as isotopic labeling studies and the measurement of kinetic isotope effects, help to outline the order of, and the barriers to, the bond-making and bond-breaking steps in these transformations. Synthetic organic chemistry is used to prepare unnatural substrates that will serve as potent enzyme inhibitors (transition state analogs) or as mechanism-based enzyme inactivators (suicide substrates). Finally, the tools of molecular biology are used to produce large quantities of enzyme and to perform site-directed mutagenesis experiments.

近期论文

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"Chan, A. C. K. ; Blair, K. M. ; Liu, Y. ; Frirdich, E. ; Gaynor, E. C. ; Tanner, M. E. ; Salama, N. R. ; Murphy, M. E. P. Helical Shape Of Helicobacter Pylori Requires An Atypical Glutamine As A Zinc Ligand In The Carboxypeptidase Csd4. JOURNAL OF BIOLOGICAL CHEMISTRY 2015, 290, 3622-3638.BibTex Tanner, M. E. Mechanistic Studies On The Indole Prenyltransferases. NATURAL PRODUCT REPORTS 2015, 32, 88-101.BibTex Awakawa, T. ; Zhang, L. ; Wakimoto, T. ; Hoshino, S. ; Mori, T. ; Ito, T. ; Ishikawa, J. ; Tanner, M. E. ; Abe, I. A Methyltransferase Initiates Terpene Cyclization In Teleocidin B Biosynthesis. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2014, 136, 9910-9913.BibTex Mahmoodi, N. ; Qian, Q. ; Luk, L. Y. P. ; Tanner, M. E. Rearrangements In The Mechanisms Of Indole Alkaloid Prenyltranferases. Pure App. Chem. 2013, 85.BibTex Liu, Y. ; Garnham, C. P. ; Roll-Mecak, A. ; Tanner, M. E. Phosphinic Acid-Based Inhibitors Of Tubulin Polyglutamylases. Bioorganic & Medicinal Chemistry Letters 2013, 23, 4408 - 4412.BibTex Mahmoodi, N. ; Tanner, M. E. Potential Rearrangements In The Reaction Catalyzed By The Indole Prenyltransferase Ftmpt1. ChemBioChem 2013, 14, 2029 - 2037.BibTex Goble, A. M. ; Toro, R. ; Li, X. ; Ornelas, A. ; Fan, H. ; Eswaramoorthy, S. ; Patskovsky, Y. ; Hillerich, B. ; Seidel, R. ; Sali, A. ; Shoichet, B. K. ; Almo, S. C. ; Swaminathan, S. ; Tanner, M. E. ; Raushel, F. M. Deamination Of 6-Aminodeoxyfutalosine In Menaquinone Biosynthesis By Distantly Related Enzymes. Biochemistry 2013, 52, 6525 - 6536.BibTex Miyafusa, T. ; Caaveiro, J. M. M. ; Tanaka, Y. ; Tanner, M. E. ; Tsumoto, K. Crystal Structure Of The Capsular Polysaccharide Synthesizing Protein Cape Of Staphylococcus Aureus. Bioscience Reports 2013, 336128294328, 463 - 474.BibTex Hadi, T. ; Hazra, S. ; Tanner, M. E. ; Blanchard, J. S. Structure Of Murnac 6-Phosphate Hydrolase (Murq) From Haemophilus Influenzae With A Bound Inhibitor. Biochemistry 2013, 52.BibTex Qian, Q. ; Schultz, A. W. ; Moore, B. S. ; Tanner, M. E. Mechanistic Studies On Cymd: A Tryptophan Reverse N -Prenyltransferase. Biochemistry 2012, 51, 7733 - 7739.BibTex Otto, N. J. ; Green, D. E. ; Masuko, S. ; Mayer, A. ; Tanner, M. E. ; Linhardt, R. J. ; Deangelis, P. L. Structure/function Analysis Of The Pasteurella Multocida Heparosan Synthases: Towards Defining Enzyme Specificity And Engineering Novel Catalysts. The Journal of biological chemistry 2012.BibTex Mayer, A. ; Gloster, T. M. ; Chou, W. K. ; Vocadlo, D. J. ; Tanner, M. E. 6""-Azido-6""-Deoxy-Udp-N-Acetylglucosamine As A Glycosyltransferase Substrate. Bioorganic & Medicinal Chemistry Letters 2011, 21, 1199 - 1201.BibTex Luk, L. Y. P. ; Qian, Q. ; Tanner, M. E. A Cope Rearrangement In The Reaction Catalyzed By Dimethylallyltryptophan Synthase?. Journal of the American Chemical Society 2011, 133, 12342 - 12345.BibTex Li, X. ; Apel, D. ; Gaynor, E. C. ; Tanner, M. E. 5’-Methylthioadenosine Nucleosidase Is Implicated In Playing A Key Role In A Modified Futalosine Pathway For Menaquinone Biosynthesis In Campylobacter Jejuni. Journal of Biological Chemistry 2011, 286, 19392 - 19398.BibTex Hadi, T. ; Pfeffer, J. M. ; Clarke, A. J. ; Tanner, M. E. Water-Soluble Substrates Of The Peptidoglycan-Modifying Enzyme O- Acetylpeptidoglycan Esterase (Ape1) From Neisseria Gonorrheae. The Journal of Organic Chemistry 2011, 76, 1118 - 1125.BibTex Li, X. ; Tanner, M. E. An Efficient Synthesis Of Futalosine. Tetrahedron Letters 2010, 51, 6463 - 6465.BibTex Kowatz, T. ; Morrison, J. P. ; Tanner, M. E. ; Naismith, J. H. The Crystal Structure Of The Y140F Mutant Of Adp-L-Glycero-D-Manno-Heptose 6-Epimerase Bound To Adp-Β-D-Mannose Suggests A One Base Mechanism. Protein Science 2010, 19, 1337 - 1343.BibTex Liu, F. ; Lee, H. J. ; Strynadka, N. C. J. ; Tanner, M. E. Inhibition Of Neisseria Meningitidis Sialic Acid Synthase By A Tetrahedral Intermediate Analogue. Biochemistry 2009, 48, 9194-9201.BibTex Luk, L. Y. P. ; Tanner, M. E. Mechanism Of Dimethylallyltryptophan Synthase: Evidence For A Dimethylallyl Cation Intermediate In An Aromatic Prenyltransferase Reaction. Journal of the American Chemical Society 2009, 131, 13932-13933.BibTex Liu, F. ; Aubry, A. J. ; Schoenhofen, I. C. ; Logan, S. M. ; Tanner, M. E. The Engineering Of Bacteria Bearing Azido-Pseudaminic Acid-Modified Flagella. Chembiochem 2009, 10, 1317-1320.BibTex