Evidence map›Paper›PMID 24301183›Full record

ArticleThe Journal of antibiotics2014

Computational identification and analysis of orphan assembly-line polyketide synthases.

Robert V O'Brien, Ronald W Davis, Chaitan Khosla, Maureen E Hillenmeyer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of antibiotics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

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  14. The biosynthetic diversity of the animal world.The Journal of biological chemistry · 2019
    Review
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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

4 authors.

Robert V O'BrienDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Ronald W Davis1] Department of Biochemistry, Stanford University, Stanford, CA, USA [2] Stanford Genome Technology Center, 855 South California Avenue, Palo Alto, CA, USA.
Chaitan Khosla1] Department of Chemistry, Stanford University, Stanford, CA, USA [2] Department of Biochemistry, Stanford University, Stanford, CA, USA [3] Chemical Engineering, Stanford University, Stanford, CA, USA.
Maureen E Hillenmeyer1] Department of Biochemistry, Stanford University, Stanford, CA, USA [2] Stanford Genome Technology Center, 855 South California Avenue, Palo Alto, CA, USA.

Funding

WHOLE YEAST GENOME TRANSCRIPTIONAL AND FUNCTIONAL GENE MAPS--A FEASIBILITY STUDYP01HG000205 · NHGRI · STANFORD UNIVERSITY · PI DAVIS, RONALD WAYNE, HOWE, ROGER THOMAS · 1990 to 2016
$120.9M
Structure, Mechanism, and Engineering of Assembly Line Polyketide SynthasesR01GM087934 · NIGMS · STANFORD UNIVERSITY · PI KHOSLA, CHAITAN · 2009 to 2021
$4.9M
A New Approach for Engineering Polyketides by Cytochrome P450 C-H OxidationF32GM103165 · NIGMS · STANFORD UNIVERSITY · PI O'BRIEN, ROBERT VINCENT · 2013 to 2014
$69k
NHGRI NIH HHS P01 HG000205NIGMS NIH HHS F32 GM103165NIGMS NIH HHS GM103165-01A1NIGMS NIH HHS R01 GM087934NIGMS NIH HHS R01 GM087936
6 · The paper itself

Abstract

The increasing availability of DNA sequence data offers an opportunity for identifying new assembly-line polyketide synthases (PKSs) that produce biologically active natural products. We developed an automated method to extract and consolidate all multimodular PKS sequences (including hybrid PKS/non-ribosomal peptide synthetases) in the National Center for Biotechnology Information (NCBI) database, generating a non-redundant catalog of 885 distinct assembly-line PKSs, the majority of which were orphans associated with no known polyketide product. Two in silico experiments highlight the value of this search method and resulting catalog. First, we identified an orphan that could be engineered to produce an analog of albocycline, an interesting antibiotic whose gene cluster has not yet been sequenced. Second, we identified and analyzed a hitherto overlooked family of metazoan multimodular PKSs, including one from Caenorhabditis elegans. We also developed a comparative analysis method that identified sequence relationships among known and orphan PKSs. As expected, PKS sequences clustered according to structural similarities between their polyketide products. The utility of this method was illustrated by highlighting an interesting orphan from the genus Burkholderia that has no close relatives. Our search method and catalog provide a community resource for the discovery of new families of assembly-line PKSs and their antibiotic products.

Indexed as

Sequence Analysis, DNAAnimalsAnti-Bacterial AgentsAutomationBase SequenceBurkholderiaCaenorhabditis elegansComputer SimulationDatabases, ProteinLactonesMultigene FamilyPolyketide SynthasesProtein EngineeringalbocyclineAnti-Bacterial AgentsLactonesPolyketide Synthases

Identifiers

PMID24301183
PMCPMC4028714

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.