Publications

There is great current interest in exploiting ribosome chemistry to generate sequence-defined chemical polymers that extend beyond L-⍺-amino acids to new backbone modifications and polymerization chemistries. Although the E. coli ribosome tolerates certain non-L-⍺-amino acids in vitro, few structural insights are available, and the boundary… Read More »New paper: Atomistic simulations of the E. coli ribosome provide selection criteria for translationally active substrates

Aminoacyl-tRNA synthetases (aaRSs) catalyze the condensation of α-amino acid monomers with tRNA. The resulting aminoacyl-tRNAs are used as substrates by the ribosome to generate natural sequence-defined bio-polymers. The ribosomal synthesis of non-natural sequence-defined bio-polymers, a major C-GEM goal, demands aaRS enzymes for monomers that are… Read More »New paper: Expanding the substrate scope of pyrrolysyl-transfer RNA synthetase enzymes to include non-α-amino acids in vitro and in vivo

Although the E. coli ribosome can incorporate a variety of non-L-α-amino acid monomers into polypeptide chains in vitro, there exists no high-resolution structural information regarding their positioning within the catalytic center of the ribosome, the peptidyl transferase center (PTC). Thus, details regarding the mechanism of… Read More »New paper: Aminobenzoic acid derivatives obstruct induced fit in the catalytic center of the ribosome

Led by C-GEM graduate student Amos Nissley in the Cate Lab, this paper describes chimeric ribosomes that incorporate sequences from certain hyperthermophilic Archaea into the E. coli ribosome. These chimeric ribosomes showed higher thermotolerance than the E. coli ribosome with no change in structure. Additionally,… Read More »New paper: Rare ribosomal RNA sequences from archaea stabilize the bacterial ribosome

Led by C-GEM postdoc Josh Walker, this paper describes the installation of thiazoline and thiazole backbone modifications in peptides and proteins, including those containing non-natural monomers. This work is a collaboration between the Schepartz and Francis labs, with contributions from Noah Hamlish, Avery Tytla, and… Read More »New paper: Redirecting RiPP Biosynthetic Enzymes to Proteins and Backbone-Modified Substrates

Genetic code expansion has tremendous potential to revolutionize peptide, protein, and protein-like therapeutics through the strategic substitution of non-canonical amino acids – or even more exotic monomers – to improve functional diversity, pharmacodynamics, produce antibody-drug conjugates, or even generate novel macrocycles. In all of these… Read More »New paper: Genetic code expansion with high yield and exceptional fidelity