Evidence map›Paper›PMID 36314667›Full record

ArticleAngewandte Chemie (International ed. in English)2023

The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis.

Andrew J Devine, Alice E Parnell, Catherine R Back, Nicholas R Lees, Samuel T Johns, Ainul Z Zulkepli, Rob Barringer, Katja Zorn, James E M Stach, Matthew P Crump and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.6field-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

5 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. β-Lactams from the Ocean.Marine drugs · 2023
    Review
  4. Article
  5. The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023
    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

14 authors at 3 institutions in 2 countries.

Andrew J DevineSchool of Chemistry, University of Bristol, BS81TS, Bristol, UK.ORCID 0000-0002-4200-5542
Alice E ParnellSchool of Biochemistry, University of Bristol, BS81TD, Bristol, UK.
Catherine R BackSchool of Biochemistry, University of Bristol, BS81TD, Bristol, UK.
Nicholas R LeesSchool of Chemistry, University of Bristol, BS81TS, Bristol, UK.
Samuel T JohnsSchool of Biochemistry, University of Bristol, BS81TD, Bristol, UK.
Ainul Z ZulkepliSchool of Biochemistry, University of Bristol, BS81TD, Bristol, UK.
Rob BarringerSchool of Biochemistry, University of Bristol, BS81TD, Bristol, UK.
Katja ZornBioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 43183, Mölndal, Sweden.
James E M StachSchool of Natural and Environmental Sciences, Newcastle University, NE17RU, Newcastle-upon-Tyne, UK.ORCID 0000-0001-8787-2407
Matthew P CrumpSchool of Chemistry, University of Bristol, BS81TS, Bristol, UK.ORCID 0000-0002-7868-5818
Martin A HayesBioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 43183, Mölndal, Sweden.
Marc W van der KampSchool of Biochemistry, University of Bristol, BS81TD, Bristol, UK.ORCID 0000-0002-8060-3359
Paul R RaceSchool of Biochemistry, University of Bristol, BS81TD, Bristol, UK.ORCID 0000-0003-0184-5630
Christine L WillisSchool of Chemistry, University of Bristol, BS81TS, Bristol, UK.ORCID 0000-0002-3919-3642
University of Bristol · GBAstraZeneca (Sweden) · SENewcastle University · GB

Funding

Biotechnology and Biological Sciences Research Council BB/L01386X/1Biotechnology and Biological Sciences Research Council BB/M012107/1Biotechnology and Biological Sciences Research Council BB/M026280/1Biotechnology and Biological Sciences Research Council BB/T001968/1Biotechnology and Biological Sciences Research Council BB/T008741/1Engineering and Physical Sciences Research Council EP/G036764/1Engineering and Physical Sciences Research Council EP/L016494/1
6 · The paper itself

Abstract

Abyssomicin C and its atropisomer are potent inhibitors of bacterial folate metabolism. They possess complex polycyclic structures, and their biosynthesis has been shown to involve several unusual enzymatic transformations. Using a combination of synthesis and in vitro assays we reveal that AbyV, a cytochrome P450 enzyme from the aby gene cluster, catalyses a key late-stage epoxidation required for the installation of the characteristic ether-bridged core of abyssomicin C. The X-ray crystal structure of AbyV has been determined, which in combination with molecular dynamics simulations provides a structural framework for our functional data. This work demonstrates the power of combining selective carbon-13 labelling with NMR spectroscopy as a sensitive tool to interrogate enzyme-catalysed reactions in vitro with no need for purification.

Indexed as

Bridged Bicyclo Compounds, HeterocyclicCytochrome P-450 Enzyme SystemMolecular Dynamics SimulationSecondary Metabolismabyssomicin CBridged Bicyclo Compounds, HeterocyclicCytochrome P-450 Enzyme SystemAntibioticsBiosynthesisP450 EnzymesPolyketidesStructure Elucidation

Identifiers

PMID36314667
PMCPMC10107801
OpenAlexW4307770903

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.