Evidence map›Paper›PMID 26631750›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases.

Grace Caldara-Festin, David R Jackson, Jesus F Barajas, Timothy R Valentic, Avinash B Patel, Stephanie Aguilar, MyChi Nguyen, Michael Vo, Avinash Khanna, Eita Sasaki and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. 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. Review
  3. An origin for a eukaryotic lipid transfer protein fold in Asgard archaea.bioRxiv : the preprint server for biology · 2025
    Article
  4. Review
  5. Analysis of the Setomimycin Biosynthetic Gene Cluster fromInternational journal of molecular sciences · 2024
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  7. Article
  8. A discrete intermediate for the biosynthesis of both the enediyne core and the anthraquinone moiety of enediyne natural products.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Article
  10. Article
  11. Structural characterization of DynU16, a START/Bet v1-like protein involved in dynemicin biosynthesis.Acta crystallographica. Section F, Structural biology communications · 2021
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. 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

12 authors.

Grace Caldara-FestinDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
David R JacksonDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697; drjackso@uci.edu sctsai@uci.edu.
Jesus F BarajasDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
Timothy R ValenticDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
Avinash B PatelDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
Stephanie AguilarDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
MyChi NguyenDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
Michael VoDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
Avinash KhannaDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697;
Eita SasakiDivision of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin, TX 78712; Department of Chemistry, University of Texas, Austin, TX 78712.
Hung-Wen LiuDivision of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin, TX 78712; Department of Chemistry, University of Texas, Austin, TX 78712.
Shiou-Chuan TsaiDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; Department of Chemistry, University of California, Irvine, CA 92697; Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697; drjackso@uci.edu sctsai@uci.edu.

Funding

Three-Membered Ring Metabolites, Inhibition &FormationR01GM040541 · NIGMS · UNIVERSITY OF TEXAS AUSTIN · PI LIU, HUNG-WEN · 1989 to 2023
$7.4M
The Ketoreduction and Cyclization of Aromatic Polyketide BiosynthesisR01GM076330 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI TSAI, SHIOU-CHUAN · 2007 to 2011
$1.3M
NIGMS NIH HHS GM040541NIGMS NIH HHS R01 GM040541NIGMS NIH HHS R01 GM076330NIGMS NIH HHS R01GM076330
6 · The paper itself

Abstract

Aromatic polyketides make up a large class of natural products with diverse bioactivity. During biosynthesis, linear poly-β-ketone intermediates are regiospecifically cyclized, yielding molecules with defined cyclization patterns that are crucial for polyketide bioactivity. The aromatase/cyclases (ARO/CYCs) are responsible for regiospecific cyclization of bacterial polyketides. The two most common cyclization patterns are C7-C12 and C9-C14 cyclizations. We have previously characterized three monodomain ARO/CYCs: ZhuI, TcmN, and WhiE. The last remaining uncharacterized class of ARO/CYCs is the di-domain ARO/CYCs, which catalyze C7-C12 cyclization and/or aromatization. Di-domain ARO/CYCs can further be separated into two subclasses: "nonreducing" ARO/CYCs, which act on nonreduced poly-β-ketones, and "reducing" ARO/CYCs, which act on cyclized C9 reduced poly-β-ketones. For years, the functional role of each domain in cyclization and aromatization for di-domain ARO/CYCs has remained a mystery. Here we present what is to our knowledge the first structural and functional analysis, along with an in-depth comparison, of the nonreducing (StfQ) and reducing (BexL) di-domain ARO/CYCs. This work completes the structural and functional characterization of mono- and di-domain ARO/CYCs in bacterial type II polyketide synthases and lays the groundwork for engineered biosynthesis of new bioactive polyketides.

Indexed as

AromataseModels, MolecularMutagenesisPolyketide SynthasesProtein ConformationAromatasePolyketide Synthasesaromatase/cyclasepolyketide biosynthesisstructural biology

Identifiers

PMID26631750
PMCPMC4687605

What OpenQuestion holds

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Registered trials

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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.