Evidence map›Paper›PMID 31610076›Full record

ArticleAngewandte Chemie (International ed. in English)2019

Characterization of a Citrulline 4-Hydroxylase from Nonribosomal Peptide GE81112 Biosynthesis and Engineering of Its Substrate Specificity for the Chemoenzymatic Synthesis of Enduracididine.

Christian R Zwick, Max B Sosa, Hans Renata

Open access · greenAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

21 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Enzymatic Peroxidation in the Chemoenzymatic Synthesis of 13-Oxoverruculogen.Synlett : accounts and rapid communications in synthetic organic chemistry · 2025
    Article
  3. Article
  4. Article
  5. Recent Progress on Peroxidase Modification and Application.Applied biochemistry and biotechnology · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Chemoenzymatic Synthesis of 13-Oxoverruculogen.Journal of the American Chemical Society · 2023
    Article
  10. Review
  11. Total Synthesis of GE81112A: An Orthoester-Based Approach.The Journal of organic chemistry · 2023
    Article
  12. Review
  13. Engineered and Artificial Metalloenzymes for Selective C-H Functionalization.Current opinion in green and sustainable chemistry · 2021
    Article
  14. Article
  15. Review
  16. Article
  17. Exploration of Iron- and a-Ketoglutarate-Dependent Dioxygenases as Practical Biocatalysts in Natural Product Synthesis.Synlett : accounts and rapid communications in synthetic organic chemistry · 2021
    Article
  18. Review
  19. Article
  20. Review
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

3 authors at 1 institution in 1 country.

Christian R ZwickDepartment of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL, 33458, USA.
Max B SosaDepartment of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL, 33458, USA.
Hans RenataDepartment of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL, 33458, USA.ORCID 0000-0003-2468-2328
Scripps Research Institute · US

Funding

Biocatalytic C-H Functionalization Logic in the Chemoenzymatic Synthesis of Therapeutic Natural ProductsR35GM128895 · NIGMS · UNIVERSITY OF FLORIDA · PI Hans Renata · 2018 to 2026
$3.7M
NIGMS NIH HHS R35 GM128895
6 · The paper itself

Abstract

The GE81112 tetrapeptides are a small family of unusual nonribosomal peptide congeners with potent inhibitory activity against prokaryotic translation initiation. With the exception of the 3-hydroxy-l-pipecolic acid unit, little is known about the biosynthetic origins of the non-proteinogenic amino acid monomers of the natural product family. Here, we elucidate the biogenesis of the 4-hydroxy-l-citrulline unit and establish the role of an iron- and α-ketoglutarate-dependent enzyme (Fe/αKG) in the pathway. Homology modelling and sequence alignment analysis further facilitate the rational engineering of this enzyme to become a specific 4-arginine hydroxylase. We subsequently demonstrate the utility of this engineered enzyme in the synthesis of a dipeptide fragment of the antibiotic enduracidin. This work highlights the value of applying a bioinformatics-guided approach in the discovery of novel enzymes and engineering of new catalytic activity into existing ones.

Indexed as

AlanineBiocatalysisCitrullineHydroxylationPeptidesPyrrolidinesSubstrate SpecificityAlanineCitrullineL-allo-enduracididinePeptidesPyrrolidinesbiocatalysisbiosynthesiscitrulline hydroxylaseenzyme engineeringnon-heme dioxygenases

Identifiers

PMID31610076
PMCPMC6917913
OpenAlexW2980348771

What OpenQuestion holds

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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.