Satish K Nair
314C Roger Adams Lab
Office: (217) 333-0641
Lab: (217) 333-2688
Fax: (217) 244-5858
Mail to: Department of Biochemistry
417 Roger Adams Lab B-4
600 S Mathews Ave
Urbana, IL 61801
Head, Department of Biochemistry
Gregorio Weber Chair
Director, Center for Biophysics & Quantitative Biology
Co-Director, Macromolecular CryoEM and MicroED Facility
Member, Institute for Genomic Biology
Affiliate, Materials Research Laboratory
Drug Discovery, Enzymology, Host-Pathogen Interactions, Membrane Biology, Microbial Physiology, Protein Structure
Disease Research Interests
Infectious Diseases, Metabolic Disorders/Diabetes
B.S. 1989 Brown University
Ph.D. 1994 University of Pennsylvania
Postdoc. 1995-99 Rockefeller University
Natural products biosynthesis, bacterial signalling, X-ray crystallography
Research in the Nair lab focuses on understanding the biosynthesis and use of bacterial natural products. We use biochemical and microbiological techniques, in combination with biophysical methods (in particular X-ray crystallography) to study how bacteria produce these small molecules and how they use these compounds to regulate intra-species behavior or to kill competing species. The development of such natural products can be used to combat the growth of pathogens including bacteria, fungi, and protozoa.
Ribosomally synthesized peptide antibiotics: A main research focus in our laboratory is on biosynthetic enzymes that modify ribosomally encoded peptides to yield macrocyclic natural products. We are specifically focused on understanding the mechanism for the synthesis of two classes of such compounds: lantibiotics and cyanobactins. For both classes of natural products, the genetic nature of the precursor and the modular architecture of the modification/processing enzymes may be exploited to yield novel molecules with improved therapeutic applications. Our work on lantibiotics, in collaboration with the laboratories of Wilfred van der Donk land Doug Mitchell (Chemistry: UIUC), has been aimed at characterization of several enzymes involved in biosynthesis. Our work on cyanobactin, in collaboration with Eric Schmidt (Medicinal Chemistry: Utah) focuses on structure-function characterization of enzymatic pathways for the production of these heterocyclized macrocyclic marine natural products.
Phosphonate biosynthesis and engineering: We are members of the Mining Microbial Genomes theme within the Institute of Genomic Biology (van Der Donk: Chemistry, Metcalf: Microbiology and Zhao: Chemical Engineering). In collaboration with the members of this theme, we are focused on characterization of enzymes involved in the biosynthesis of phosphonate antibiotics, with the aim of using the structural data to reprogram these enzymes to produce novel compounds.
Bacterial inter- and intracellular communication: Bacteria can utilize small molecules as signals and we are focusing on elucidating the mechanisms underlying this process. In quorum sensing, bacteria coordinate population growth by utilizing small molecule inducers (typically acylhomoserine lactones). When the population density exceeds some threshold, these autoinducers bind to their cognate receptor and activate the transcription of various genes. A second class of inter-cellular communication is predicated upon the action of a diffusible signal factors that are chemically distinct from quorum sensing autoinducers. In theory, as each of these pathways are regulated by small molecules, they represent ideal targets for therapeutic intervention against bacterial growth.
Simon, M.A., Ongpipattanakul, C., Nair, S.K., and van der Donk, W.A. (2021) “Biosynthesis of fosftomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily.” Proc. Nat’l. Acad. Sci.,118, e2019863118.
Liu, A., Si, Y., Dong, S.H., Mahanta, N., Penkala, H.N., Nair, S.K. and Mitchell, D.A. (2021) “Functional elucidation of TfuA in peptide backbone thioamidation.” Nature Chem. Bio., 17, 585-92.
Cogan, D.P., Ly, J., and Nair, S.K. (2020) “Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation.” ACS Chem. Bio., 15, 2783-91.
Kapoor, I., Olivares, P., and Nair, S.K. (2020) “Biochemical basis for the regulation of biosynthesis of antiparasitics by bacterial hormones.” eLife, doi:10.7554/eLife.57824.
Dong, S.H., Cogan, D.P., and Nair, S.K. (2020) “Structural Biology of RiPP Natural Products Biosynthesis.” Comprehensive Natural Products III: Chemistry and Biology, doi:10.1016/B978-0-12-409547-2.14686-4.
Dong, S.H., Nhu-Lam, M., Nagarajan, R., and Nair, S.K. (2020) “Structure-guided biochemical analysis of quorum signal synthase specificities.” ACS Chem Biology, doi:10.1021/acschembio.0c00142.
Chekan, J., Ongpipattanakul, C., and Nair, S.K. (2019) “Steric complementarity directs sequence promiscuous leader binding in RiPP biosynthesis.” Proc. Natl. Acad. Sci. 116, 24049-55.
Bothwell, I.R., Cogan, D.P., Kim, T., Reinhardt, C.J., van der Donk, W.A.(*), and Nair, S.K.(*) (2019) “Characterization of glutamyl-tRNA-dependent dehydratases using nonreactive substrate mimics.” Proc. Natl. Acad. Sci. 116, 17245-250.
Chekan, J., Ongpipattanakul, C., Wright, T.R., Zhang, B., Bollinger, J.M., Rajakovich, L.J., Crebs, C.M., Cicchillo, R.M., and Nair, S.K. (2019) “Molecular basis for enantioselective herbicide degradation imparted by aryloxyalkanoate dioxygenases in transgenic plants.” Proc. Natl. Acad. Sci. 116, 13299-304.