Evidence map›Paper›PMID 33440167›Full record

ArticleCell chemical biology2021

Re-wiring the regulation of the formicamycin biosynthetic gene cluster to enable the development of promising antibacterial compounds.

Rebecca Devine, Hannah P McDonald, Zhiwei Qin, Corinne J Arnold, Katie Noble, Govind Chandra, Barrie Wilkinson, Matthew I Hutchings

Abstract read
In one paragraph

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Review
  2. Article
  3. Interactions at theMicrobiology (Reading, England) · 2026
    Review
  4. Article
  5. Review
  6. Microbe Profile:Microbiology (Reading, England) · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. An unusual aromatase/cyclase programs the formation of the phenyldimethylanthrone framework in anthrabenzoxocinones and fasamycin.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Review
  17. Article
  18. 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

8 authors.

Rebecca DevineDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: rebecca.devine@jic.ac.uk.
Hannah P McDonaldDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Zhiwei QinDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Corinne J ArnoldDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Katie NobleDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Govind ChandraDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Barrie WilkinsonDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: barrie.wilkinson@jic.ac.uk.
Matthew I HutchingsDepartment of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: matt.hutchings@jic.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/M011216/1Biotechnology and Biological Sciences Research Council BB/S00811X/1Biotechnology and Biological Sciences Research Council BB/S009000/1Biotechnology and Biological Sciences Research Council BBS/E/J/000PR9790
6 · The paper itself

Abstract

The formicamycins are promising antibiotics first identified in Streptomyces formicae KY5, which produces the compounds at low levels. Here, we show that by understanding the regulation of the for biosynthetic gene cluster (BGC), we can rewire the BGC to increase production levels. The for BGC consists of 24 genes expressed on nine transcripts. The MarR regulator ForJ represses expression of seven transcripts encoding the major biosynthetic genes as well as the ForGF two-component system that initiates biosynthesis. We show that overexpression of forGF in a ΔforJ background increases formicamycin production 10-fold compared with the wild-type. De-repression, by deleting forJ, also switches on biosynthesis in liquid culture and induces the production of additional, previously unreported formicamycin congeners. Furthermore, combining de-repression with mutations in biosynthetic genes leads to biosynthesis of additional bioactive precursors.

Indexed as

Anti-Bacterial AgentsMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsMolecular StructureMultigene FamilyStreptomycesAnti-Bacterial Agentsantibioticsbiosynthesisfasamycinsformicamycinsnatural productsregulationStreptomycestwo-component system

Identifiers

PMID33440167
PMCPMC8062789

What OpenQuestion holds

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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.