Shanteri Singh
Associate 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, 1996RESEARCH:
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.
Selected Publications:
Johnson, B. P., Mandal, P. S., Brown, S. M., Thomas, L. M.,, and Singh, S.(2024) Ternary complexes of isopentenyl phosphate kinase from Thermococcus paralvinellae reveal molecular determinants of non-natural substrate specificity. Proteins DOI: 10.1002/prot.26674.
Gardner, E. D., Johnson, B. P., Dimas, D. A., McClurg, H. E., Severance, Z. C., Burgett, A. W., and Singh, S.(2023) Unlocking new prenylation modes: Azaindoles as a new substrate class for indole prenyltransferases. ChemCatChem 15(19), DOI:10.1002/cctc.202300650.
Johnson, B. P., Kumar, V., Scull, E. M., Thomas, L. M., Bourne, C. R., and Singh, S.(2022) Molecular basis for the substrate promiscuity of isopentenyl phosphate kinase from Candidatus methanomethylophilus alvus. ACS Chem Biol 17: 85–102.
Kumar, V., Johnson, B. P., Dimas, D. A., and Singh, S. (2021) Novel homologs of isopentenyl phosphate kinase reveal class-wide substrate flexibility. ChemCatChem 13: 3781-3788.
Scull, E. M., Bandari, C., Johnson, B. P., Gardner, E. D., Tonelli, M., You, J., Cichewicz, R. H., and Singh, S. (2020) Chemoenzymatic synthesis of daptomycin analogs active against daptomycin resistant strains. Appl. Microbiol. and Biotechnol. 104:7853-7865.
Gardner, E. D., Dimas, D. A., Finneran, M. C., Brown, S. M., Burgett, A. W. and Singh, S. (2020) Indole C6 functionalization of tryprostatin B using prenyltransferase CdpNPT. Catalysts 10: 1247.
Johnson, B. P., Scull, E. M., Dimas, D. A., Bavineni, T., Batchev, A. L., Bandari, C., Gardner, E. D., Nimmo, S. L., and Singh, S. (2020) Acceptor substrate determines donor specificity of an aromatic prenyltransferase: expanding the biocatalytic potential of NphB. Appl. Microbiol. and Biotechnol. 104:4383-4395.
Bandari, C., Scull, E. M., Bavineni, T., Nimmo, S. L., Gardner, E. D., Bensen, R. C., Burgett, A. W., and Singh, S. (2019) FgaPT2, a biocatalytic tool for alkyl-diversification of indole natural products. Medchemcomm. 2019, 10:1465-1475.
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.