Publications

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)

C-GEM researchers developed a novel method called 3-Prime Adenosine-Retaining Aminoacyl–tRNA Isolation (PARTI), which determines precisely how much of a cellular tRNA is acylated, what it is acylated with, and whether it has been acylated once or twice. PARTI is an essential verification tool for optimizing… Read More »Breakthrough Article: Monitoring monomer-specific acyl–tRNA levels in cells with PARTI (Nucleic Acids Res, 2025)

C-GEM researchers developed a novel post-translational backbone editing reaction to replace a peptide bond with a C-C bond as diketones and heterocycles. This general strategy provides the first example of a C–C bond forming reaction to take place within the peptide backbone, as well as… Read More »Peptide Backbone Editing via Post-Translational O to C Acyl Shift (JACS, 2025)

C-GEM researchers found that a single atom change on tRNA—O to S on the 3′ terminal adenosine—does not hinder regular translation. Changing the 3’ oxo-ester on tRNA to a more reactive thioester had the potential to impact translation positively or negatively at multiple steps in… Read More »Thioesters Support Efficient Protein Biosynthesis by the Ribosome (ACS Cent Sci, 2025)

C-GEM researchers investigated whether preventing the binding of ribosomal protein bS1 could improve ribosome orthogonality. A current, common strategy for generating orthogonal ribosomes involves controlling mRNA and ribosome interactions by modifying the Shine-Dalgarno and anti-Shine-Dalgarno sequences, the sequence that sits upstream of the start codon… Read More »Role of Ribosomal Protein bS1 in Orthogonal mRNA Start Codon Selection (Biochemistry, 2025)

C-GEM researchers developed a fast, simple, and generalizable method to assay aminoacyl-tRNA synthetase activity by detecting the acylated tRNA product using liquid chromatography–mass spectrometry. C-GEM first developed this method as a way to identify aminoacyl-tRNA synthetase enzymes that accept non-α-amino acid substrates even at extremely… Read More »Direct and quantitative analysis of tRNA acylation using intact tRNA liquid chromatography–mass spectrometry (Nat Protoc, 2025)

C-GEM published a new paper in Nature Communications in collaboration with the Innovative Genomics Institute. Our researchers developed an RNA language model to predict mutations that could lead to improved structural stability. This model was used to predict mutations that could lead to improved thermostability… Read More »RNA language models predict mutations that improve RNA function (Nat Commun, 2024)