Ribosome-mediated polymerization of long chain carbon and cyclic amino acids into peptides in vitro

Joongoo Lee, Kevin J Schwarz, Do Soon Kim, Jeffrey S Moore, Michael C Jewett

Research output: Contribution to journalArticlepeer-review

Abstract

Ribosome-mediated polymerization of backbone-extended monomers into polypeptides is challenging due to their poor compatibility with the translation apparatus, which evolved to use α-L-amino acids. Moreover, mechanisms to acylate (or charge) these monomers to transfer RNAs (tRNAs) to make aminoacyl-tRNA substrates is a bottleneck. Here, we rationally design non-canonical amino acid analogs with extended carbon chains (γ-, δ-, ε-, and ζ-) or cyclic structures (cyclobutane, cyclopentane, and cyclohexane) to improve tRNA charging. We then demonstrate site-specific incorporation of these non-canonical, backbone-extended monomers at the N- and C- terminus of peptides using wild-type and engineered ribosomes. This work expands the scope of ribosome-mediated polymerization, setting the stage for new medicines and materials.

Original languageEnglish (US)
Pages (from-to)4304
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Aug 27 2020

Keywords

  • Amino Acids, Cyclic/metabolism
  • Genetic Engineering
  • Mutation
  • Peptide Biosynthesis
  • Polymerization
  • RNA, Transfer/metabolism
  • Ribosomes/genetics
  • Transfer RNA Aminoacylation

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