Contact Information
University of Illinois
361 RAL, Box 22-5
600 South Mathews Avenue
Urbana, IL 61801
Biography
Professor Mitchell received his undergraduate degree in chemistry from Carnegie Mellon University in 2002. After a short internship in medicinal chemistry at Merck Research Laboratories, he moved to the University of California, Berkeley and worked with Michael Marletta. After earning his PhD in 2006, Professor Mitchell pursued postdoctoral studies with Jack Dixon at the University of California, San Diego. Professor Mitchell joined the University of Illinois faculty in 2009 and has research interests that span the interface of chemistry and biology.
Research Interests
reactivity-based natural product discovery; complex molecule structural elucidation and derivatization; structure-activity relationships and mode of action determination of biomedically important compounds; natural product chemical biology: mechanistic enzymology of key biosynthetic enzymes; structure-function studies of complex small molecules; and development of bioinformatic and bioorganic methodology to accelerate the discovery of biomedically important compounds
Research Description
Our primary objective is to use a blend of chemical and biological approaches to address the alarming rise in antibiotic resistance. In this endeavour, we seek to identify and characterize novel antibiotic compounds. Our research involves the characterization of novel natural products and employs synthetic methods to reveal both biological mode of action and structure-activity relationships. Further, we evaluate the mechanistic details of key biosynthetic enzymes for the purposes of analog generation. Taken together, our work aims to expedite the discovery of future medicines from biological sources. Of special interest are compounds that only kill pathogenic bacteria or directly target mechanisms of virulence. Unlike currently deployed antibiotics, which exclusively target essential life processes, our strategy holds great potential in delaying resistance. The Mitchell laboratory is a multidisciplinary team that draws methodology from the fields of chemical biology, organic chemistry, microbiology, pharmacology, structural biology, and bioinformatics.
For a more detailed research description see: https://mitchell-lab.chemistry.illinois.edu/index.html
Awards and Honors
2015 National Fresenius Award, Phi Lambda Upsilon (National Chemistry Honor Society)
2015 Camille Dreyfus Teacher-Scholar Award
2015-2016 Helen Corley Petit Scholar (UIUC College of Liberal Arts and Sciences)
2015 Pfizer Award in Enzyme Chemistry (ACS Division of Biological Chemistry)
Tomorrow's PI: Genome Technology magazine
Packard Fellowship in Science and Engineering
NIH Director's New Innovator Award
Additional Campus Affiliations
John & Margaret Witt Professor, Chemistry
Professor, Chemistry
Professor, Carl R. Woese Institute for Genomic Biology
Affiliate, Microbiology
External Links
Recent Publications
Nguyen, D. T., Mitchell, D. A., & van der Donk, W. A. (Accepted/In press). Genome Mining for New Enzyme Chemistry. ACS Catalysis, 4536-4553. https://doi.org/10.1021/acscatal.3c06322
Chadwick, G. L., Joiner, A. M. N., Ramesh, S., Mitchell, D. A., & Nayak, D. D. (2023). McrD binds asymmetrically to methyl-coenzyme M reductase improving active-site accessibility during assembly. Proceedings of the National Academy of Sciences of the United States of America, 120(25), Article e2302815120. https://doi.org/10.1073/pnas.2302815120
Kretsch, A. M., Gadgil, M. G., Dicaprio, A. J., Barrett, S. E., Kille, B. L., Si, Y., Zhu, L., & Mitchell, D. A. (2023). Peptidase Activation by a Leader Peptide-Bound RiPP Recognition Element. Biochemistry, 62(4), 956-967. https://doi.org/10.1021/acs.biochem.2c00700
Precord, T. W., Ramesh, S., Dommaraju, S. R., Harris, L. A., Kille, B. L., & Mitchell, D. A. (2023). Catalytic Site Proximity Profiling for Functional Unification of Sequence-Diverse Radical S-Adenosylmethionine Enzymes. ACS Bio and Med Chem Au, 3(3), 240-251. https://doi.org/10.1021/acsbiomedchemau.2c00085
Ren, H., Dommaraju, S. R., Huang, C., Cui, H., Pan, Y., Nesic, M., Zhu, L., Sarlah, D., Mitchell, D. A., & Zhao, H. (2023). Genome mining unveils a class of ribosomal peptides with two amino termini. Nature communications, 14(1), Article 1624. https://doi.org/10.1038/s41467-023-37287-1