Expanded ribosomal synthesis of non-standard cyclic backbones in vitro

Kanghun Lee, Hyeongwoo Park, Ravi Kumar Devarapalli, Dahye Im, Jongcheol Seo and Joongoo Lee ()
Additional contact information
Kanghun Lee: Pohang University of Science and Technology (POSTECH)
Hyeongwoo Park: Pohang University of Science and Technology (POSTECH)
Ravi Kumar Devarapalli: Pohang University of Science and Technology (POSTECH)
Dahye Im: Pohang University of Science and Technology (POSTECH)
Jongcheol Seo: Pohang University of Science and Technology (POSTECH)
Joongoo Lee: Pohang University of Science and Technology (POSTECH)

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract The ribosome polymerizes L-α-amino acids into polypeptides, catalyzing peptide bond formation through aminolysis. This process is facilitated by entropy trapping within its peptidyl transferase center (PTC). In this research, we harness this capability to synthesize polymers containing cyclic motifs in the backbone. We design 26 non-canonical monomers (ncMs) with two distinct substrates: dicarboxylic esters and hydrazinoesters, each containing bifunctional moieties that undergo ring-closing reactions through multiple aminolysis reactions. Using a cell-free system that enables the consecutive incorporation of these ncMs into a growing peptide, we discover that the ribosome can produce 5- and 6-membered cyclic backbones, which have never been reported. We also demonstrate that the formation of such cyclic backbones within the ribosome is tunable by altering the substituents of dicarboxylic esters. This discovery expands the range of non-standard backbones that can be synthesized by the ribosome and motivates future research towards expanding ribosome-mediated chemistries for biopolymer synthesis.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60126-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60126-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60126-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().