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

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 ?-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 (?-, ?-, ?-, and ?-) 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.

SUBMITTER: Lee J

PROVIDER: S-EPMC7452890 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Lee Joongoo J Schwarz Kevin J KJ Kim Do Soon DS Moore Jeffrey S JS Jewett Michael C MC

Nature communications 20200827 1

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 cyclo ...[more]

PMID: 32855412

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