Evidence map›Paper›PMID 24746560›Full record

ArticleChemistry & biology2014

Specificity and promiscuity at the branch point in gentamicin biosynthesis.

Junhong Guo, Fanglu Huang, Chuan Huang, Xiaobo Duan, Xinyun Jian, Finian Leeper, Zixin Deng, Peter F Leadlay, Yuhui Sun

Open access · hybridAbstract read
In one paragraph

Article in Chemistry & biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.0field-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

22 citing papers in PubMed, 84 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Glycodiversification of gentamicins throughActa pharmaceutica Sinica. B · 2024
    Article
  6. Facile and selectiveGreen chemistry : an international journal and green chemistry resource : GC · 2022
    Article
  7. Article
  8. (mLife · 2022
    Article
  9. Engineering ofMolecules (Basel, Switzerland) · 2021
    Article
  10. Article
  11. Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  12. Article
  13. Exclusive Production of Gentamicin C1a fromAntibiotics (Basel, Switzerland) · 2019
    Article
  14. Overproduction of gentamicin B in industrial strainMetabolic engineering communications · 2019
    Article
  15. Article
  16. Article
  17. Article
  18. Methyltransferases of gentamicin biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  19. Review
  20. 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

9 authors at 2 institutions in 2 countries.

Junhong GuoKey Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and School of Pharmaceutical Sciences, Wuhan University, Wuhan, Wuchang 430071, People's Republic of China.
Fanglu HuangDepartment of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
Chuan HuangKey Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and School of Pharmaceutical Sciences, Wuhan University, Wuhan, Wuchang 430071, People's Republic of China.
Xiaobo DuanKey Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and School of Pharmaceutical Sciences, Wuhan University, Wuhan, Wuchang 430071, People's Republic of China.
Xinyun JianKey Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and School of Pharmaceutical Sciences, Wuhan University, Wuhan, Wuchang 430071, People's Republic of China.
Finian LeeperDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Zixin DengKey Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and School of Pharmaceutical Sciences, Wuhan University, Wuhan, Wuchang 430071, People's Republic of China.
Peter F LeadlayDepartment of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK. Electronic address: pfl10@cam.ac.uk.
Yuhui SunKey Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), and School of Pharmaceutical Sciences, Wuhan University, Wuhan, Wuchang 430071, People's Republic of China. Electronic address: yhsun@whu.edu.cn.
Wuhan University · CNUniversity of Cambridge · GB

Funding

Biotechnology and Biological Sciences Research Council B18119Medical Research Council G1001687
6 · The paper itself

Abstract

Gentamicin C complex is a mixture of aminoglycoside antibiotics used to treat severe Gram-negative bacterial infections. We report here key features of the late-stage biosynthesis of gentamicins. We show that the intermediate gentamicin X2, a known substrate for C-methylation at C-6' to form G418 catalyzed by the radical SAM-dependent enzyme GenK, may instead undergo oxidation at C-6' to form an aldehyde, catalyzed by the flavin-linked dehydrogenase GenQ. Surprisingly, GenQ acts in both branches of the pathway, likewise oxidizing G418 to an analogous ketone. Amination of these intermediates, catalyzed mainly by aminotransferase GenB1, produces the known intermediates JI-20A and JI-20B, respectively. Other pyridoxal phosphate-dependent enzymes (GenB3 and GenB4) act in enigmatic dehydroxylation steps that convert JI-20A and JI-20B into the gentamicin C complex or (GenB2) catalyze the epimerization of gentamicin C2a into gentamicin C2.

Indexed as

BiocatalysisCarbohydrate ConformationCarbohydrate SequenceGentamicinsMethyltransferasesMolecular Sequence DataSubstrate SpecificityGentamicinsMethyltransferases

Identifiers

PMID24746560
PMCPMC4039129
OpenAlexW2076105307

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.