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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 27, 2020
- Source ID
- 10.1038/s41467-020-18001-x
Entities
People
- Do Soon Kim
- Jeffrey S. Moore
- Joongoo Lee
- Kevin J. Schwarz
- Michael C Jewett
Organizations
- Army Research Office
- National Science Foundation