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Shanteri SinghAssistant Professor, Chemistry and Biochemistry Office: Stephenson Life Sciences Research Center 2190 Lab: Stephenson Life Sciences Research Center 2150 405-325-2088 shanteri dot singh at ou dot edu https://www.ou.edu/cas/chemistry/directory/faculty/shanteri-singh Ph.D., Structural Biology-Tata Inst. of Fundamental Research, 1996
Natural products, the secondary metabolites of plants and microorganisms, constitute a significant part of all approved drugs. Natural product diversification involves modification of the molecular skeleton of natural products to generate analogs with altered activities for their potential biotechnological use including drug development. Many natural products are structurally complex, and chemical modifications of such molecules can be challenging. Chemoenzymatic natural product diversification presents an attractive alternative, that exploits the relaxed substrate specificity of biocatalysts (enzymes) to modify complex natural products in a regio- and stereo- selective manner. The focus of research in Singh group is to develop tools, and reagents for chemoenzymatic natural product diversification strategies for developing drugs against cancer, infectious diseases and neurological disorders. Our research lies at the interface of chemistry and biology, that involves synthetic chemistry, enzymology, biochemistry and structural biology. We characterize new enzymes from natural product biosynthetic pathway, study their structure at molecular level using X-ray crystallography, engineer variant enzymes with altered/enhanced activity for their utility as biocatalysts for the generation of pharmaceutically relevant molecules.
Bandari, C., Scull, E. M., Masterson, J. M., Tran, R. H. Q., Foster, S. B., Nicholas, K. M., and Singh. S. (2017) Determination of Alkyl-Donor Promiscuity of Tyrosine-O-Prenyltransferase SirD from Leptosphaeria maculans. ChemBioChem. 8: 2323-2327.
Elshahawi, S. I., Cao, H., Shaaban, K. A., Ponomareva, L. V., Subramanian, T., Farman, M. L., Spielmann, H. P., Phillips, G. N., Jr., Thorson, J. S., and Singh, S. (2017) Structure and specificity of a permissive bacterial C-prenyltransferase. Nat Chem Biol. 13: 366-368.
Huber, T. D., Wang, F., Singh, S., Johnson, B. R., Sunkara, M., Van Lanen, S. G., Morris, A. J., Phillips, G. N., Jr., and Thorson, J. S. (2016) Functional AdoMet isosteres resistant to classical AdoMet degradation pathways. ACS Chem. Biol. 11: 2484-2491.
Han, L., Singh, S., Thorson, J. S., and Phillips, G. N., Jr. (2016) Loop dynamics of thymidine diphosphate-rhamnose 3'-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis. Struct. Dyn. 3: 012004.
Cao, H., Tan, K., Wang, F., Bigelow, L., Yennamalli, R. M., Jedrzejczak, R., Babnigg, G., Bingman, C. A., Joachimiak, A., Kharel, M. K., Singh, S., Thorson, J. S., and Phillips, G. N., Jr. (2016) Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate. Struct. Dyn. 3: 034702.
Singh, S., Kim, Y., Wang, F., Bigelow, L., Endres, M., Kharel, M. K., Babnigg, G., Bingman, C. A., Joachimiak, A., Thorson, J. S., and Phillips, G. N., Jr. (2015) Structural characterization of AtmS13, a putative sugar aminotransferase involved in indolocarbazole AT2433 aminopentose biosynthesis. Proteins 83: 1547-1554.
Singh, S., Michalska, K., Bigelow, L., Endres, M., Kharel, M. K., Babnigg, G., Yennamalli, R. M., Bingman, C. A., Joachimiak, A.,Thorson, J. S., and Phillips, G. N., Jr. (2015) Structural characterization of CalS8, a TDP-a-D-glucose dehydrogenase involved in calicheamicin aminodideoxypentose biosynthesis. J. Biol. Chem. 290: 26249-26258.
Peltier-Pain, P., Singh, S., and Thorson, J. S. (2015) Characterization of early enzymes involved in TDP-aminodideoxypentose biosynthesis en route to AT2433. Chembiochem 16: 2141-2146.
Wang, F., Singh, S., Kim, Y., Xu, W., Helmich, K. E., Miller, M. D., Cao, H., Bingman, C. A., Thorson, J. S., and Phillips, G. N., Jr. (2015) The structural basis for the stereochemical control of amine installation in nucleotide sugar aminotransferases. ACS Chem. Biol. 10: 2048-2056.
Singh, S., Peltier-Pain, P., Tonelli, M., and Thorson, J. S. (2014) A general NMR-based strategy for the in-situ characterization of sugar nucleotide-dependent biosynthetic pathways. Org. Lett. 16: 3220-3223.