Publications

The templated synthesis of proteins containing non-canonical and expanded backbone monomers (collectively called nnAAs) promises to vastly expand the chemical space available to biological therapeutics and materials, but existing technologies remain limiting. Addressing these limitations requires a deeper understanding of how the translational mechanism is… Read More »New paper: β-amino acids reduce ternary complex stability and alter the translation elongation mechanism

Aminoacyl-tRNA synthetases (aaRSs) catalyze the condensation of ɑ-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 demands aaRS enzymes for non-natural monomers. Current aaRS engineering platforms rely… Read More »New paper: A translation-independent directed evolution strategy to engineer aminoacyl-tRNA synthetases

The ribosome is a ribonucleoprotein complex found in all domains of life. Its role is to catalyze protein synthesis, the messenger RNA (mRNA)-templated formation of amide bonds between α-amino acid monomers. Amide bond formation occurs within a highly conserved region of the large ribosomal subunit… Read More »New paper: Minimization of the E. coli ribosome, aided and optimized by community science 

One common way to isolate ribosomes produced in vivo is by installing an MS2 affinity tag in the 16S or 23S ribosomal RNA. RNA tags in the 23S rRNA are typically installed into an extended helix 98, as this has no discernible effect on growth… Read More »New paper: Interactions between terminal RNA helices affect the stability of the Escherichia coli large ribosomal subunit

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