University of Illinois
361 RAL, Box 22-5
600 South Mathews Avenue
Urbana, IL 61801
Additional Campus Affiliations
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.
genomics-guided natural product discovery; natural product structure and function elucidation; natural product chemical biology: mechanistic and biosynthetic enzyme chemistry; peptide engineering; synthetic biology
We are a chemical biology group that focuses on the study of natural products. Natural products are highly evolved and functionally privileged compounds that often display complex chemical structures. These molecules have inspired generations of synthetic organic chemists, unveiled numerous fundamental biological processes as chemical probes, and served as the most significant source of chemical matter for drug discovery.
As the field of genomics has expanded, it has revealed a vast untapped wealth of natural products encoded in the DNA of sequenced organisms, particularly bacteria. Our lab has developed new tools to expedite the discovery of natural products from genomic data, including molecules from bacteria that cannot be cultivated in a lab. In particular, our lab focuses on Ribosomally synthesized and Post-translationally modified Peptides (RiPPs) which have genetically encoded substrates and an incredible diversity of post-translational modifications. Using a genes-to-molecule approach, we have uncovered numerous structurally unique RiPP molecules and revealed the unprecedented mechanistic enzymology through which they form. We then leverage the new biosynthetic knowledge to produce new-to-nature compounds with improved or novel activities with the long-term goal of unleashing the full biosynthetic potential of Nature to reshape the diagnosis and treatment of human disease.
For a more detailed research description see: https://mitchell-lab.chemistry.illinois.edu/index.html
Honors & Awards
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
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
Shelton, K. E., & Mitchell, D. A. (2023). Bioinformatic prediction and experimental validation of RiPP recognition elements. In A. K. Shukla (Ed.), Integrated Methods in Protein Biochemistry: Part B (pp. 191-233). (Methods in Enzymology; Vol. 679). Academic Press Inc.. https://doi.org/10.1016/bs.mie.2022.08.050
Ayikpoe, R. S., Shi, C., Battiste, A. J., Eslami, S. M., Ramesh, S., Simon, M. A., Bothwell, I. R., Lee, H., Rice, A. J., Ren, H., Tian, Q., Harris, L. A., Sarksian, R., Zhu, L., Frerk, A. M., Precord, T. W., van der Donk, W. A., Mitchell, D. A., & Zhao, H. (2022). A scalable platform to discover antimicrobials of ribosomal origin. Nature communications, 13(1), Article 6135. https://doi.org/10.1038/s41467-022-33890-w