Evidence map›Paper›PMID 35713415›Full record

ArticleJournal of the American Chemical Society2022

Accessing Diverse Pyridine-Based Macrocyclic Peptides by a Two-Site Recognition Pathway.

Dinh T Nguyen, Tung T Le, Andrew J Rice, Graham A Hudson, Wilfred A van der Donk, Douglas A Mitchell

Open access · hybridAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Repositioning the Leader Peptide in Graspetide Biosynthesis.Journal of the American Chemical Society · 2026
    Article
  4. Modular Synthesis of Pyritide-Inspired Macrocycles Featuring Bipyridine Motifs.Angewandte Chemie (International ed. in English) · 2025
    Article
  5. Article
  6. Peptidic Tryptophan Halogenation by a Promiscuous Flavin-Dependent Enzyme.Angewandte Chemie (International ed. in English) · 2025
    Article
  7. Article
  8. Review
  9. Substrate recognition by a peptide-aminoacyl-tRNA ligase.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Advances on the biosynthesis of pyridine rings.Engineering microbiology · 2023
    Review
  17. Bioinspired Total Synthesis of Pyritide A2 through Pyridine Ring Synthesis.Angewandte Chemie (International ed. in English) · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Dinh T NguyenDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0002-2101-6808
Tung T LeDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0003-0278-0955
Andrew J RiceDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0001-8794-3826
Graham A HudsonDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0002-3715-4279
Wilfred A van der DonkDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0002-5467-7071
Douglas A MitchellDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0002-9564-0953
Howard Hughes Medical Institute · USUniversity of Illinois Urbana-Champaign · US

Funding

Training Program in Chemistry-Interface with BiologyT32GM070421 · NIGMS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI HERGENROTHER, PAUL · 2005 to 2019
$5.4M
Enzyme Chemistry and Biological Function of RiPP-like Modifications.R01GM097142 · NIGMS · VANDERBILT UNIVERSITY · PI MITCHELL, DOUGLAS ALAN · 2012 to 2024
$4.1M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM097142NIGMS NIH HHS T32 GM070421
6 · The paper itself

Abstract

Macrocyclic peptides are sought-after molecular scaffolds for drug discovery, and new methods to access diverse libraries are of increasing interest. Here, we report the enzymatic synthesis of pyridine-based macrocyclic peptides (pyritides) from linear precursor peptides. Pyritides are a recently described class of ribosomally synthesized and post-translationally modified peptides (RiPPs) and are related to the long-known thiopeptide natural products. RiPP precursors typically contain an N-terminal leader region that is physically engaged by the biosynthetic proteins that catalyze modification of the C-terminal core region of the precursor peptide. We demonstrate that pyritide-forming enzymes recognize both the leader region and a C-terminal tripeptide motif, with each contributing to site-selective substrate modification. Substitutions in the core region were well-tolerated and facilitated the generation of a wide range of pyritide analogues, with variations in macrocycle sequence and size. A combination of the pyritide biosynthetic pathway with azole-forming enzymes was utilized to generate a thiazole-containing pyritide (historically known as a thiopeptide) with no similarity in sequence and macrocycle size to the naturally encoded pyritides. The broad substrate scope of the pyritide biosynthetic enzymes serves as a future platform for macrocyclic peptide lead discovery and optimization.

Indexed as

Biological ProductsPeptidesBiosynthetic PathwaysPeptides, CyclicProtein BiosynthesisProtein Processing, Post-TranslationalPyridinesBiological ProductsPeptidesPeptides, CyclicPyridines

Identifiers

PMID35713415
PMCPMC9247985
OpenAlexW4283068131

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.