Publications

NSF C-GEM researchers and collaborators found that mutating the exit tunnel of the ribosome allows it to accommodate larger monomers that previously would have gotten stuck, stalling the translation process.  Read more about the paper on the NSF C-GEM blog, where co-first author Dr. Chandrima… Read More »Altering the E. coli Ribosome Exit Tunnel to Improve Consecutive Incorporation of Challenging Monomers (ACS Cent Sci, 2026)

NSF C-GEM researchers and collaborators found a novel pathway for protein labeling using engineered aminoacyl-tRNA Synthetases (aaRS) and non-canonical amino acids (ncAAs). In the absence of their cognate tRNAs, engineered aaRSs can release reactive ncAA-AMP intermediates that covalently label nearby proteins. This system for proximity-dependent… Read More »Repurposing Engineered Aminoacyl-tRNA Synthetases for Proximity-Dependent Protein Labeling through the Release of Aminoacyl-AMP Intermediate (ACS Chem Biol, 2026)

By Alexandra Kent The goal of C-GEM is to generate ribosomally synthesized, sequence-defined polymers using a diverse set of non-natural monomers. Although ribosomes are known to incorporate some unnatural monomers, the basis for observed differences in incorporation efficiencies of different stereoisomers remains poorly understood. In… Read More »Co-Translational Incorporation of (R)- and (S)-β2-Hydroxy Acids In Vitro: A Structural and Biochemical Study on the E. coli Ribosome (J Am Chem Soc, 2026)

By Chintan Soni Proteins are powerful and versatile molecules with immense potential in medicine and the materials industry, but they are built from just 20 natural α-amino acids, linked through an α- amide backbone, limiting the range diversity of structures and functions they can achieve.… Read More »Co-Translational Incorporation of (R)- and (S)-β2-Hydroxyacids In Vivo: Directed Evolution of Efficient Aminoacyl-tRNA Synthetases (J Am Chem Soc, 2026)

Many genetic code expansion (GCE) techniques rely on the native ability that some organisms have to recode the stop codon TAG to incorporate pyrrolysine, a special amino acid not encoded in other organisms. Previously, in known organisms with this ability, pyrrolysine was only incorporated at… Read More »An archaeal genetic code with all TAG codons as pyrrolysine. (Science, 2025)

Most scientists have a complex love/hate relationship with peptides, especially in the field of drug discovery. Peptides are encodable, for sure, but they are also structurally featureless and often display exceptionally poor bioavailability and cell permeability. In this work, C-GEM researchers developed chemistry with the… Read More »Chemical and ribosomal synthesis of atropisomeric and macrocyclic peptides with embedded quinolines (Nat Chem, 2025)

Researchers at the NSF Center for Genetically Encoded Materials (C-GEM) developed a novel and versatile chemo-ribosomal strategy to generate isolable quantities of protein-derived biopolymers containing site-specific backbone modifications. This strategy relies on an intramolecular backbone-extension acyl rearrangement (BEAR) reaction that post-translationally and site-specifically rearranges the… Read More »Site-selective protein editing by backbone extension acyl rearrangements (Nat Chem Biol, 2025)

By Joshua Davisson Better Flexizyme reactions! This paper describes a method to improve the yields of flexizyme-promoted tRNA aminoacylation in vitro. Inspired by possible origins of life reaction conditions, performing flexizyme reactions in an ice eutectic phase reduces some of the critical disadvantages of flexizyme… Read More »High Yield, Low Magnesium Flexizyme Reactions in a Water-Ice Eutectic Phase (Biochemistry 2025)

By Amos Nissley C-GEM researchers identified archaeal ribosomes with highly divergent peptidyl transferase centers (PTC). Cryo-EM structures of the Pyrobaculum calidifontis ribosome revealed that unique archaeal ribosomal protein (rProtein) sequences reorganize the PTC, enabling rRNA sequence variation. Modifying E. coli rProteins to resemble those in… Read More »Structure of an archaeal ribosome reveals a divergent active site and hibernation factor (Nat Microbiol, 2025)