Organic synthesis, continuous directed evolution, enzyme biocatalysis, chemical biology
Enzymes perform complex and selective chemistry on all scales, assembling the molecules of life in every organism and synthesizing important small-molecule drugs in industrial reactors. My research group seeks to understand how nature catalyzes its most selective chemistry and how we can use those principles to unlock new enzymatic reactions in the laboratory. We build small-molecule biosensing circuits in E. coli to detect small-molecule ligands in high throughput, enabling continuous directed evolution of proteins that bind and transform small molecules.
Mercer, J. A. M.*; DeCarlo, S. J.*; Roy Burman, S. S.*; Sreekanth, V.; Nelson, A. T.; Hunkeler, M.; Chen, P. J.; Donovan, K. A.; Kokkonda, P.; Tiwari, P. K.; Shoba, V. M.; Deb, A.; Choudhary, A.; Fischer, E. S.; Liu, D. R. Continuous evolution of compact protein degradation tags regulated by selective cereblon molecular glues. Science 2024, 383, eadk4422. 10.1126/science.adk4422
Nguyen, T. M.; Sreekanth, V.; Deb, A.; Kokkonda, P.; Tiwari, P. K.; Donovan, K. A.; Shoba, V.; Chaudhary, S. K.; Mercer, J. A. M.; Lai, S.; Sadagopan, A.; Jan, M.; Fischer, E. S.; Liu, D. R.; Ebert, B. L.; Choudhary, A. Proteolysis Targeting Chimeras With Reduced Off-Targets. Nat. Chem. 2024, 16, 218–228. 10.1038/s41557-023-01379-8
Lee, G. R.; Pellock, S. J.; Norn, C.; Tischer, D.; Dauparas, J.; Anischenko, I.; Mercer, J. A. M.; Kang, A.; Bera, A.; Nguyen, H.; Goreshnik, I.; Vafeados, D.; Roullier, N; Han, H. L.; Coventry, B.; Haddox, H. K.; Liu, D. R.; Yeh, A. H.-W.; Baker, D. Small-molecule binding and sensing with a designed protein family. Preprint 2023 10.1101/2023.11.01.565201
Anzalone, A. V.; Gao, X. D.; Podracky, C. J.; Nelson, A. T.; Koblan, L. W.; Raguram, A.; Levy, J. M.; Mercer, J. A. M.; Liu, D. R. Programmable Deletion, Replacement, Integration and Inversion of Large DNA Sequences with Twin Prime Editing. Nat. Biotechnol. 2022, 40, 731–740. 10.1038/s41587-021-01133-w