Evidence map›Paper›PMID 26598135›Full record

ArticleNature communications2015

Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway.

Wai Shun Mak, Stephen Tran, Ryan Marcheschi, Steve Bertolani, James Thompson, David Baker, James C Liao, Justin B Siegel

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Advances in biosynthesis of higher alcohols in Escherichia coli.World journal of microbiology & biotechnology · 2023
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Quantifying the taxonomic bias in enzymology.Protein science : a publication of the Protein Society · 2021
    Article
  18. Enzyme engineering andSynthetic biology (Oxford, England) · 2021
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Wai Shun MakDepartment of Chemistry, University of California Davis, One Shields Avenue, Davis, California 95616, USA.
Stephen TranDepartment of Bioinformatics, University of California, Los Angeles, 172 Boyer Hall Box 951570, 611 Charles E. Young Drive East, Los Angeles, California 90095-1570, USA.
Ryan MarcheschiDepartment of Chemical and Biomolecular Engineering, University of California Los Angeles, 5531 Boelter Hall, Los Angeles, California 90095-1592, USA.
Steve BertolaniDepartment of Chemistry, University of California Davis, One Shields Avenue, Davis, California 95616, USA.
James ThompsonDepartment of Biochemistry, University of Washington, 1705 NE Pacific St Seattle, Washington 98195-7350, USA.
David BakerDepartment of Biochemistry, University of Washington, 1705 NE Pacific St Seattle, Washington 98195-7350, USA.
James C LiaoDepartment of Chemical and Biomolecular Engineering, University of California Los Angeles, 5531 Boelter Hall, Los Angeles, California 90095-1592, USA.
Justin B SiegelDepartment of Chemistry, University of California Davis, One Shields Avenue, Davis, California 95616, USA.

Funding

Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
NO as a Sensor of Gene Expression Differences: Application to Synthetic BiologyF32GM099277 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARCHESCHI, RYAN JOSEPH · 2011 to 2012
$92k
NHGRI NIH HHS T32 HG002536NIGMS NIH HHS 5F32GM099277-02NIGMS NIH HHS F32 GM099277
6 · The paper itself

Abstract

The ability to biosynthetically produce chemicals beyond what is commonly found in Nature requires the discovery of novel enzyme function. Here we utilize two approaches to discover enzymes that enable specific production of longer-chain (C5-C8) alcohols from sugar. The first approach combines bioinformatics and molecular modelling to mine sequence databases, resulting in a diverse panel of enzymes capable of catalysing the targeted reaction. The median catalytic efficiency of the computationally selected enzymes is 75-fold greater than a panel of naively selected homologues. This integrative genomic mining approach establishes a unique avenue for enzyme function discovery in the rapidly expanding sequence databases. The second approach uses computational enzyme design to reprogramme specificity. Both approaches result in enzymes with >100-fold increase in specificity for the targeted reaction. When enzymes from either approach are integrated in vivo, longer-chain alcohol production increases over 10-fold and represents >95% of the total alcohol products.

Indexed as

Computational BiologyGenomicsAlcoholsBiosynthetic PathwaysEscherichia coliKeto AcidsModels, MolecularAlcoholsKeto Acids

Identifiers

PMID26598135
PMCPMC4673503

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.