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Satish K. Nair

Head and Gregorio Weber Chair, Department of Biochemistry
Director, Center for Biophysics & Quantitative Biology

Research Interests

Research Topics

Drug Discovery, Enzymology, Host-Pathogen Interactions, Membrane Biology, Microbial Physiology, Protein Structure

Disease Research Interests

Infectious Diseases, Metabolic Disorders/Diabetes

Research Description

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.


B.S. 1989 Brown University
Ph.D. 1994 University of Pennsylvania
Postdoc. 1995-99 Rockefeller University

Highlighted Publications

Representative Publications

Pei, Z-F., Zhu, L., and Nair, S.K. (2023) “Core-dependent post-translational modifications guide the biosynthesis of a new class of hyper modified peptides.” Nature Comm. 14, 7734.

Hernandez Garcia, A., and Nair, S.K. (2023) “Structure and Function of a Class III Metal-Independent Lanthipeptide Synthetase.” ACS Cent. Sci. 9, 1944-56.

Ju, S., Kuzelka, K.P., Guo, R., Krohn-Hansen, B., Wu, L., Nair, S.K.,* and Yang, Y.* (2023) “A biocatalytic platform for the asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases.” Nature Comm. 14, 5704.(*Corresponding author)

Zheng, Y., and Nair, S.K. (2022) "YcaO-mediated ATP-dependent peptidase activity in ribosomal peptide biosynthesis." Nature Chem. Biol. doi:10.1038/s41589-022-01141-0.

Pei, Z-F., Zhu, L., Sarksian, R., van der Donk, W.A., and Nair, S.K. (2022) “Class V lanthipeptide cyclase directs the biosynthesis of a stapled peptide natural product.” J. Am. Chem. Soc. 144, 17549-57.

Ongpipattanakul, C., Desormeaux, E.K., DiCaprio, A., van der Donk, W.A.*, Mitchell, D.A.*, and Nair, S.K.* (2022) “Mechanism of action of ribosomal synthesized and post-translationally modified peptide.” Chemical Reviews 122, 14722-14814. (*Corresponding author)

Cogan, D.P., Bhushan, A., Reyes, R., Zhu, L., Piel, J., and Nair, S.K. (2022) “Structure and mechanism for iterative amide N-methylation in the biosynthesis of channel-forming peptide cytotoxins.” Proc. Nat’l. Acad. Sci. doi:10.1073/pnas.2116578119.

Zheng, Y., Cong, Y., Schmidt, E.W., and Nair, S.K. (2022) “Catalysts for the enzymatic lipidation of peptides.” Acc. Chem. Res. doi:10.1021/acs.accounts.2c00108.

Recent Publications

Chaban, A., Minakhin, L., Goldobina, E., Bae, B., Hao, Y., Borukhov, S., Putzeys, L., Boon, M., Kabinger, F., Lavigne, R., Makarova, K. S., Koonin, E. V., Nair, S. K., Tagami, S., Severinov, K., & Sokolova, M. L. (2024). Tail-tape-fused virion and non-virion RNA polymerases of a thermophilic virus with an extremely long tail. Nature communications, 15(1), Article 317.

Hernandez Garcia, A., & Nair, S. K. (2023). Structure and Function of a Class III Metal-Independent Lanthipeptide Synthetase. ACS Central Science, 9(10), 1944-1956.

Ju, S., Kuzelka, K. P., Guo, R., Krohn-Hansen, B., Wu, J., Nair, S. K., & Yang, Y. (2023). A biocatalytic platform for asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases. Nature communications, 14(1), Article 5704.

Lei, R., Hernandez Garcia, A., Tan, T. J. C., Teo, Q. W., Wang, Y., Zhang, X., Luo, S., Nair, S. K., Peng, J., & Wu, N. C. (2023). Mutational fitness landscape of human influenza H3N2 neuraminidase. Cell Reports, 42(1), Article 111951.

Ongpipattanakul, C., Liu, S., Luo, Y., Nair, S. K., & Van der donk, W. A. (2023). The mechanism of thia-Michael addition catalyzed by LanC enzymes. Proceedings of the National Academy of Sciences, 120(3), Article e2217523120.

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