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

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

  • Nat Commun. 2020 Aug 27;11(1):4304. doi: 10.1038/s41467-020-18001-x.
Joongoo Lee # 1,  Kevin J Schwarz # 2,  Do Soon Kim 1,  Jeffrey S Moore 3 4,  Michael C Jewett 5
Affiliations

Affiliations

  • 1 Department of Chemical and Biological Engineering and Center for Synthetic Biology, Northwestern University, Evanston, IL, 60208, USA.
  • 2 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
  • 3 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. jsmoore@illinois.edu.
  • 4 The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. jsmoore@illinois.edu.
  • 5 Department of Chemical and Biological Engineering and Center for Synthetic Biology, Northwestern University, Evanston, IL, 60208, USA. m-jewett@northwestern.edu.
  • # Contributed equally.
PMID: 32855412 DOI: 10.1038/s41467-020-18001-x
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.

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