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The supramolecular chemistry of the antibiotic Teixobactin – how basic research on a new antibiotic has provided new insights and exciting opportunities

Séminaire Chimie ED459

Prof. James S. Nowick, Distinguished Professor (Depts of Chemistry and Pharmaceutical Sciences, University of California Irvine, CA, USA)

Le Jeudi 11 Mai 2023 à 14h

ENSCM, Amphithéâtre Godechot (240 av. Émile-Jeanbrau)

Date de début : 2023-05-11 14:00:00

Date de fin : 2023-05-11 15:30:00

Lieu : ENSCM amphi Godechot (240 av E. Jeanbrau)

Intervenant : Prof. James S. Nowick, Distinguished Professor

Departments of Chemistry and Pharmaceutical Sciences, University of California Irvine, CA, USA

This lecture will describe how my laboratory’s efforts to study the recently discovered antibiotic teixobactin led to a new understanding how this antibiotic achieves its remarkable biological activity. Initial efforts to synthesize teixobactin analogues and perform structure-activity relationship studies showed us that active teixobactin analogues undergo supramolecular self-assembly. X-ray crystallography then provided insights into the supramolecular interactions that impart biological activity. Fluorescence microscopy has allowed us to probe these interactions on the surface of Gram-positive bacteria. Ongoing efforts inspired by what we have learned from teixobactin have now afforded a new class of antibiotics with improved properties, termed “isobactins.”

Selected references

– “Elucidation of the Teixobactin Pharmacophore.” H. Yang, K. H. Chen, J. S. Nowick, ACS Chem. Biol. 2016, 11, 1823–1826.

– “Alanine Scan Reveals Modifiable Residues in Teixobactin.” K. H. Chen, S. P. Le, X. Han, J. M. Frias, J. S. Nowick, Chem. Commun. 2017, 53, 11357-11359.

– “X-ray Crystallographic Structure of a Teixobactin Derivative Reveals Amyloid-Like Assembly.” H. Yang, M. Wierzbicki, D. R. Du Bois, J. S. Nowick, J. Am. Chem. Soc. 2018, 140, 14028–14032.

– “Design, Synthesis, and Study of Lactam and Ring-Expanded Analogues of Teixobactin.” H. Yang, A. V. Pishenko, X. Li, J. S. Nowick, J. Org. Chem. 2020, 85, 1331–1339.

– “A Fluorescent Teixobactin Analogue.” M. A. Morris, M. Malek, M. H. Hashemian, B. T. Nguyen, S. Manuse, K. Lewis, J. S. Nowick, ACS Chem. Biol. 2020, 15, 1222–1231.

– “Visualizing the Mode of Action and Supramolecular Assembly of Teixobactin Analogues in Bacillus subtilis.” M. A. Morris, A. Vallmitjana, F. Grein, T. Schneider, M. Arts, C. R. Jones, B. T. Nguyen, M. H. Hashemian, M. Malek, E. Gratton, J. S. Nowick, Chemical Science 2022, 13, 7747–7754.

– “Teixobactin Kills Bacteria by a Two-Pronged Attack on the Cell Envelope.” R. Shukla, F. Lavore, S. Maity, M. G. N. Derks, C. R. Jones, B. J. A.Vermeulen, A. Melcrová, M. A. Morris, L. M. Becker, X. Wang, R. Kumar, J. Medeiros-Silva, R. A. M. van Beekveld, A. M. J. J. Bonvin, J. Lorent, M. Lelli, J. S. Nowick, H. D. MacGillavry, A. J. Peoples, A. L. Spoering, L. L. Ling, D. E. Hughes, W. H. Roos, E. Breukink, K. Lewis, M. Weingarth, Nature 2022, 608, 390–396.

– “Isobactins: O-Acyl Isopeptide Prodrugs of Teixobactin and Teixobactin Derivatives.” C. R. Jones, G. Guaglianone, G. H. Lai, J. S. Nowick, Chemical Science 2022, 13, 13110–13116.


James Nowick received his Bachelors degree in Chemistry in 1985 from Columbia University and his Ph.D. degree in Organic Chemistry in 1990 from MIT, where he was both an NSF Graduate Fellow and an ACS Division of Organic Chemistry Graduate Fellow. After an NSF postdoctoral fellowship in supramolecular chemistry at MIT, he began his independent career as an Assistant Professor at UCI in 1991. He was promoted to Associate Professor in 1996 and Professor in 1998. Professor Nowick served as Chair of the Department of Chemistry from 2016-2019. He is currently a Distinguished Professor in the Department of Chemistry and the Department of Pharmaceutical Sciences.

Professor Nowick’s research interests include bioorganic chemistry and chemical biology; molecular recognition and supramolecular chemistry; and peptide and protein structure. Current efforts in his research laboratory are focused on understanding the molecular basis of Alzheimer’s disease and other amyloid diseases and the development of antibiotics.

With his group members, Professor Nowick has published more than 140 papers to date. In recognition of his scientific contributions, he has received a Camille and Henry Dreyfus Foundation New Faculty Award, an American Cancer Society Junior Faculty Research Award, an NSF Young Investigator Award, an Arnold and Mabel Beckman Foundation Young Investigator Award, a Presidential Faculty Fellow Award, a Camille Dreyfus Teacher-Scholar Award, an Alfred P. Sloan Research Fellowship, and an American Chemical Society Arthur C. Cope Scholar Award. He is a Fellow of the American Association for the Advancement of Science and the American Chemical Society. For his contributions to research and education at UCI, he has received the Award for Outstanding Faculty Contribution to Undergraduate Research, the Chancellor’s Award for Excellence in Undergraduate Research, and the School of Physical Sciences Award for Outstanding Contributions to Undergraduate Education.

Professor Nowick is well known by students for his video-based education content on YouTube, which consists of more than 100 hours of video lectures of his classes: Organic Chemistry, Advanced Organic Chemistry, and Organic Spectroscopy. Some of his lectures have received more than 100,000 views. Working with the Dean of the School of Physical Sciences and the Dean of Continuing Education, Distance Learning, and Summer Session, Professor Nowick helped found UCI’s Open Chemistry initiative, to make an even wider variety of UCI’s Chemistry courses available in full video format. In recognition of his contributions, Professor Nowick has received the Creative Innovation Award for Open Education Excellence from the Open Education Consortium.

Contact local IBMM : Dr. Muriel Amblard, D.R. CNRS (DAPP équipe F9)