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

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.

Citation

Joongoo Lee, Kevin J Schwarz, Do Soon Kim, Jeffrey S Moore, Michael C Jewett. Ribosome-mediated polymerization of long chain carbon and cyclic amino acids into peptides in vitro. Nature communications. 2020 Aug 27;11(1):4304

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PMID: 32855412

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