Research in the Charkoudian Lab:
Applying bioorganic chemistry, biophysics, and biochemistry to understand and discover new ways to make molecules.
We are interested in studying how nature creates structurally complex molecules. Currently, we are asking two fundamental questions with direct applications to make novel molecules to better human health and the environment.
We are grateful to the following funding agencies for believing in us!! NSF (CAREER), NIH (R15), Research Corporation for Science Advancement (Cottrell Scholars Award).
How does nature drive chemical innovation? And can we use history as a roadmap for future engineering efforts?
In collaboration with Dr. Maureen Hillenmeyer (HexagonBio), we recently unveiled key mechanisms that nature uses to drive chemical diversity, and identified fertile ground for the discovery of novel antibiotics. We are now using this history as a roadmap for rational engineering efforts, and mining unexplored regions of the phylogenetic tree to uncover molecules of novel structure and function.
Want to learn more? Check out these relevant papers!
- Fuga Li, Y., Tsai, K., Harvey, C., Ary, B., Berlew, E., Boehman, B., Findley, D., Friant, A., Gardner, C., Gould, M., Ha, J.H., Lilley, B., McKinstry, E., Nawal, S., Parry, R., Rothchild, K., Silbert, S., Tentilucci, M., Thurston, A., Wai, R., Yoon, Y., Aiyar, R., Medema, M. H., Hillenmeyer, M. E., and Charkoudian, L. K.* “Comprehensive Curation and Analysis of Fungal Biosynthetic Gene Clusters of Published Natural Products.” Fungal Genet. & Biol., 2016. 89, 18-28.
- Hillenmeyer, M. H., Borisova, G. V., Berlew, E. E., Charkoudian, L. K. “Evolution of Chemical Diversity by Coordinated Gene Swaps in Type II Polyketide Gene Clusters.” Proc. Natl. Acad. Sci. 2015, 112, 13952 – 13957.
How do proteins communicate to build complicated molecules? And can we use this information to mix-and-match proteins from different biosynthetic pathways to make novel molecules?
We are interested in understanding how microorganisms use enzyme assemblies to make important pharmaceutical agents. We are developing innovative approaches to study the transient protein-protein and protein-substrate interactions, including site-specific vibrational spectroscopy (with Dr. Casey Londergan) and analytical ultracentrifugation (with Dr. Robert Fairman). We are now leveraging these techniques, along with traditional biochemical approaches, to characterize the molecular interactions of carrier proteins that are central to functioning natural product synthases.
Most relevant recent publications:
- Thiele, G. A. R., Friedman, C. P., Tsai, K. J. S., Beld, J., Londergan, C. H., Charkoudian, L. K. "Acyl Carrier Protein Cyanylation Delivers Ketoacyl Synthase-Carrier Protein Cross-link." Biochemistry 2017, 56, 2533-2536.
- Kokona, B., Winesett, E. S., von Krusenstiern, A. N., Cryle, M. J., Fairman, R. Charkoudian, L. K. “Probing the Selectivity of Beta-hydroxylation Reactions in Non-ribosomal Peptide Synthesis using Analytical Ultracentrifugation.” Anal. Biochem. 2016, 495, 42-51.
- Johnson, M. N. R., Londergan, C. H., Charkoudian, L. K. “Probing the Phosphopantetheine Arm Conformations of Acyl Carrier Proteins using Vibrational Spectroscopy.” J. Am. Chem. Soc. 2014, 136, 11240-11243. (Article highlighted in C&EN News)
- Email: email@example.com
- Office: KINSC E214A
- Phone: (610) 896-2994
- Office Hours: TBA