Evidence map›Paper›PMID 26783060›Full record

ArticleAngewandte Chemie (International ed. in English)2016

Production of New Cladosporin Analogues by Reconstitution of the Polyketide Synthases Responsible for the Biosynthesis of this Antimalarial Agent.

Rachel V K Cochrane, Randy Sanichar, Gareth R Lambkin, Béla Reiz, Wei Xu, Yi Tang, John C Vederas

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2016. 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
4.8field-weighted citation impact, top 5% 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, 49 citations in OpenAlex.

  1. Article
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  9. Article
  10. Review
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  12. Aminoacyl-tRNA synthetases as therapeutic targets.Nature reviews. Drug discovery · 2019
    Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Polyphasic taxonomy ofStudies in mycology · 2017
    Article
  18. Article
  19. Review
  20. Metabolomics-guided analysis of isocoumarin production byMetabolomics : Official journal of the Metabolomic Society · 2016
    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

7 authors at 2 institutions in 2 countries.

Rachel V K CochraneDepartment of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada).
Randy SanicharDepartment of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada).
Gareth R LambkinDepartment of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada).
Béla ReizDepartment of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada).
Wei XuDepartment of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA).
Yi TangDepartment of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA).
John C VederasDepartment of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada). john.vederas@ualberta.ca.
University of Alberta · CAUniversity of California, Los Angeles · US

Funding

Rediscovering Natural Chemical Diversity -1DP1GM106413DP1GM106413 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TANG, YI · 2012 to 2016
$3.9M
Characterization and Engineering of Fungal Megasynthases in Escherichia coliR01GM085128 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TANG, YI · 2008 to 2016
$2.1M
NCCDPHP CDC HHS 1DP1 GM106413NIGMS NIH HHS 1R01 GM085128NIGMS NIH HHS DP1 GM106413NIGMS NIH HHS R01 GM085128
6 · The paper itself

Abstract

The antimalarial agent cladosporin is a nanomolar inhibitor of the Plasmodium falciparum lysyl-tRNA synthetase, and exhibits activity against both blood- and liver-stage infection. Cladosporin can be isolated from the fungus Cladosporium cladosporioides, where it is biosynthesized by a highly reducing (HR) and a non-reducing (NR) iterative type I polyketide synthase (PKS) pair. Genome sequencing of the host organism and subsequent heterologous expression of these enzymes in Saccharomyces cerevisiae produced cladosporin, confirming the identity of the putative gene cluster. Incorporation of a pentaketide intermediate analogue indicated a 5+3 assembly by the HR PKS Cla2 and the NR PKS Cla3 during cladosporin biosynthesis. Advanced-intermediate analogues were synthesized and incorporated by Cla3 to furnish new cladosporin analogues. A putative lysyl-tRNA synthetase resistance gene was identified in the cladosporin gene cluster. Analysis of the active site emphasizes key structural features thought to be important in resistance to cladosporin.

Indexed as

AntimalarialsIsocoumarinsPolyketide SynthasesAntimalarialscladosporinIsocoumarinsPolyketide Synthasesantimalarial agentsbiosynthesiscladosporinheterologous expressionpolyketides

Identifiers

PMID26783060
PMCPMC4906947
OpenAlexW2178127499

What OpenQuestion holds

Textmetadata
LicenceTDM
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.