Nair, Satish K. - University of Illinois at Urbana-Champaign -

个人简介

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

研究领域

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.

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Designer installation of a substrate recruitment domain to tailor enzyme specificity Park, R., Ongpipattanakul, C., Nair, S. K., Bowers, A. A. & Kuhlman, B., Apr 2023, In: Nature chemical biology. 19, 4, p. 460-467 8 p. Mutational fitness landscape of human influenza H3N2 neuraminidase 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., Jan 31 2023, In: Cell Reports. 42, 1, 111951. The mechanism of thia-Michael addition catalyzed by LanC enzymes Ongpipattanakul, C., Liu, S., Luo, Y., Nair, S. K. & Van der donk, W. A., Jan 17 2023, In: Proceedings of the National Academy of Sciences. 120, 3, e2217523120. YcaO-mediated ATP-dependent peptidase activity in ribosomal peptide biosynthesis Zheng, Y. & Nair, S. K., Jan 2023, In: Nature chemical biology. 19, 1, p. 111-119 9 p. Bioconjugate Platform for Iterative Backbone N-Methylation of Peptides Zheng, Y., Ongpipattanakul, C. & Nair, S. K., Nov 18 2022, In: ACS Catalysis. 12, 22, p. 14006-14014 9 p. Catalysts for the Enzymatic Lipidation of Peptides Zheng, Y., Cong, Y., Schmidt, E. W. & Nair, S. K., May 3 2022, In: Accounts of chemical research. 55, 9, p. 1313-1323 11 p. Class v Lanthipeptide Cyclase Directs the Biosynthesis of a Stapled Peptide Natural Product Pei, Z. F., Zhu, L., Sarksian, R., Van Der Donk, W. A. & Nair, S. K., Sep 28 2022, In: Journal of the American Chemical Society. 144, 38, p. 17549-17557 9 p. Control of Nucleophile Chemoselectivity in Cyanobactin YcaO Heterocyclases PatD and TruD Gu, W., Zheng, Y., Pogorelov, T., Nair, S. K. & Schmidt, E. W., May 20 2022, In: ACS chemical biology. 17, 5, p. 1215–1225 Convergent and divergent biosynthetic strategies towards phosphonic acid natural products Ju, K. S. & Nair, S. K., Dec 2022, In: Current Opinion in Chemical Biology. 71, 102214. Enzymatic Pyridine Aromatization during Thiopeptide Biosynthesis Rice, A. J., Pelton, J. M., Kramer, N. J., Catlin, D. S., Nair, S. K., Pogorelov, T. V., Mitchell, D. A. & Bowers, A. A., Nov 23 2022, In: Journal of the American Chemical Society. 144, 46, p. 21116-21124 9 p. Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides Ongpipattanakul, C., Desormeaux, E. K., Dicaprio, A., Van Der Donk, W. A., Mitchell, D. A. & Nair, S. K., Sep 28 2022, In: Chemical reviews. 122, 18, p. 14722-14814 93 p. Prevalence and mechanisms of evolutionary contingency in human influenza H3N2 neuraminidase Lei, R., Tan, T. J. C., Hernandez Garcia, A., Wang, Y., Diefenbacher, M., Teo, C., Gopan, G., Tavakoli Dargani, Z., Teo, Q. W., Graham, C. S., Brooke, C. B., Nair, S. K. & Wu, N. C., Dec 2022, In: Nature communications. 13, 1, 6443. Structure and mechanism for iterative amide N-methylation in the biosynthesis of channel-forming peptide cytotoxins Cogan, D. P., Bhushan, A., Reyes, R., Zhu, L., Piel, J. & Nair, S. K., Mar 29 2022, In: Proceedings of the National Academy of Sciences of the United States of America. 119, 13, e2116578119. Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily Simon, M. A., Ongpipattanakul, C., Nair, S. K. & van der Donk, W. A., Jun 8 2021, In: Proceedings of the National Academy of Sciences of the United States of America. 118, 23, e2019863118. Characterization of a Glyphosate-Tolerant Enzyme from Streptomyces svecius: A Distinct Class of 5-Enolpyruvylshikimate-3-phosphate Synthases Griffin, S. L., Chekan, J. R., Lira, J. M., Robinson, A. E., Yerkes, C. N., Siehl, D. L., Wright, T. R., Nair, S. K. & Cicchillo, R. M., May 5 2021, In: Journal of Agricultural and Food Chemistry. 69, 17, p. 5096-5104 9 p. Functional elucidation of TfuA in peptide backbone thioamidation Liu, A., Si, Y., Dong, S. H., Mahanta, N., Penkala, H. N., Nair, S. K. & Mitchell, D. A., May 2021, In: Nature chemical biology. 17, 5, p. 585-592 8 p. Identification and characterization of andalusicin: N-terminally dimethylated class III lantibiotic from Bacillus thuringiensis sv. andalousiensis Grigoreva, A., Andreeva, J., Bikmetov, D., Rusanova, A., Serebryakova, M., Garcia, A. H., Slonova, D., Nair, S. K., Lippens, G., Severinov, K. & Dubiley, S., May 21 2021, In: iScience. 24, 5, 102480. LanCLs add glutathione to dehydroamino acids generated at phosphorylated sites in the proteome Lai, K. Y., Galan, S. R. G., Zeng, Y., Zhou, T. H., He, C., Raj, R., Riedl, J., Liu, S., Chooi, K. P., Garg, N., Zeng, M., Jones, L. H., Hutchings, G. J., Mohammed, S., Nair, S. K., Chen, J., Davis, B. G. & van der Donk, W. A., May 13 2021, In: Cell. 184, 10, p. 2680-2695.e26 New developments in RiPP discovery, enzymology and engineering Montalbán-López, M., Scott, T. A., Ramesh, S., Rahman, I. R., van Heel, A. J., Viel, J. H., Bandarian, V., Dittmann, E., Genilloud, O., Goto, Y., Grande Burgos, M. J., Hill, C., Kim, S., Koehnke, J., Latham, J. A., Link, A. J., Martínez, B., Nair, S. K., Nicolet, Y., Rebuffat, S., & 16 others, 2021, In: Natural Product Reports. 38, 1, p. 130-239 110 p. Structural and mechanistic investigations of protein S-glycosyltransferases Fujinami, D., Garcia de Gonzalo, C. V., Biswas, S., Hao, Y., Wang, H., Garg, N., Lukk, T., Nair, S. K. & van der Donk, W. A., Dec 16 2021, In: Cell chemical biology. 28, 12, p. 1740-1749.e6 Biochemical basis for the regulation of biosynthesis of antiparasitics by bacterial hormones Kapoor, I., Olivares, P. & Nair, S. K., Jun 2020, In: eLife. 9, p. 1-33 33 p., e57824. Characterization of a Dehydratase and Methyltransferase in the Biosynthesis of Ribosomally Synthesized and Post-translationally Modified Peptides in Lachnospiraceae Huo, L., Zhao, X., Acedo, J. Z., Estrada, P., Nair, S. K. & van der Donk, W. A., Jan 15 2020, In: ChemBioChem. 21, 1-2, p. 190-199 10 p. Functional interactions between posttranslationally modified amino acids of methyl-coenzyme M reductase in Methanosarcina acetivorans Nayak, D. D., Liu, A., Agrawal, N., Rodriguez-Carerro, R., Dong, S. H., Mitchell, D. A., Nair, S. K. & Metcalf, W. W., Feb 2020, In: PLoS biology. 18, 2, e3000507. Interception of the Bycroft-Gowland Intermediate in the Enzymatic Macrocyclization of Thiopeptides Bogart, J. W., Kramer, N. J., Turlik, A., Bleich, R. M., Catlin, D. S., Schroeder, F. C., Nair, S. K., Williamson, R. T., Houk, K. N., Bowers, A. A. & Bowers, A. A., Jul 29 2020, In: Journal of the American Chemical Society. 142, 30, p. 13170-13179 10 p. Natural product biosynthesis: What’s next? An introduction to the JBC Reviews Thematic Series Nair, S. K. & Jez, J. M., Jan 10 2020, In: Journal of Biological Chemistry. 295, 2, p. 335-336 2 p. Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation Cogan, D. P., Ly, J. & Nair, S. K., Oct 16 2020, In: ACS chemical biology. 15, 10, p. 2783-2791 9 p. Structural Biology of RiPP Natural Products Biosynthesis Dong, S-H., Cogan, D. P. & Nair, S. K., 2020, Comprehensive Natural Products III. Liu, H-W. & Begley, T. P. (eds.). 3 ed. Elsevier, Vol. 2. p. 17-48 Structure-Guided Biochemical Analysis of Quorum Signal Synthase Specificities Dong, S. H., Nhu-Lam, M., Nagarajan, R. & Nair, S. K., Jun 19 2020, In: ACS chemical biology. 15, 6, p. 1497-1504 8 p. Biosynthesis of the RiPP trojan horse nucleotide antibiotic microcin C is directed by the N-formyl of the peptide precursor Dong, S. H., Kulikovsky, A., Zukher, I., Estrada, P., Dubiley, S., Severinov, K. & Nair, S. K., Feb 28 2019, In: Chemical Science. 10, 8, p. 2391-2395 5 p. Characterization of glutamyl-tRNA–dependent dehydratases using nonreactive substrate mimics Bothwell, I. R., Cogan, D. P., Kim, T., Reinhardt, C. J., van der Donk, W. A. & Nair, S. K., Aug 27 2019, In: Proceedings of the National Academy of Sciences of the United States of America. 116, 35, p. 17245-17250 6 p. Characterization of the flavin monooxygenase involved in biosynthesis of the antimalarial FR-900098 Nguyen, K., DeSieno, M. A., Bae, B., Johannes, T. W., Cobb, R. E., Zhao, H. & Nair, S. K., 2019, In: Organic and Biomolecular Chemistry. 17, 6, p. 1506-1518 13 p. Insights into AMS/PCAT transporters from biochemical and structural characterization of a double glycine motif protease Bobeica, S. C., Dong, S. H., Huo, L., Mazo, N., McLaughlin, M. I., Jiménez-Osés, G., Nair, S. K. & van der Donk, W. A., 2019, In: eLife. 8, e42305. Mechanistic Basis for Ribosomal Peptide Backbone Modifications Dong, S. H., Liu, A., Mahanta, N., Mitchell, D. A. & Nair, S. K., May 22 2019, In: ACS Central Science. 5, 5, p. 842-851 10 p. Molecular basis for enantioselective herbicide degradation imparted by aryloxyalkanoate dioxygenases in transgenic plants Chekan, J. R., Ongpipattanakul, C., Wright, T. R., Zhang, B., Martin Bollinger, J., Rajakovich, L. J., Krebs, C., Cicchillo, R. M. & Nair, S. K., 2019, In: Proceedings of the National Academy of Sciences of the United States of America. 116, 27, p. 13299-13304 6 p. Molecular Basis of Bacillus subtilis ATCC 6633 Self-Resistance to the Phosphono-oligopeptide Antibiotic Rhizocticin Petronikolou, N., Ortega, M. A., Borisova, S. A., Nair, S. K. & Metcalf, W. W., Apr 19 2019, In: ACS chemical biology. 14, 4, p. 742-750 9 p. Reiterative synthesis by the ribosome and recognition of the N-terminal formyl group by biosynthetic machinery contribute to evolutionary conservation of the length of antibiotic microcin c peptide precursor Zukher, I., Pavlov, M., Tsibulskaya, D., Kulikovsky, A., Zyubko, T., Bikmetov, D., Serebryakova, M., Nair, S. K., Ehrenberg, M., Dubiley, S. & Severinova, K., Mar 1 2019, In: mBio. 10, 2, e00768-19. Steric complementarity directs sequence promiscuous leader binding in RiPP biosynthesis Chekan, J. R., Ongpipattanakul, C. & Nair, S. K., Nov 26 2019, In: Proceedings of the National Academy of Sciences of the United States of America. 116, 48, p. 24049-24055 7 p.