Evidence map›Paper›PMID 31611640›Full record

ArticleNature microbiology2019

CRAGE enables rapid activation of biosynthetic gene clusters in undomesticated bacteria.

Gaoyan Wang, Zhiying Zhao, Jing Ke, Yvonne Engel, Yi-Ming Shi, David Robinson, Kerem Bingol, Zheyun Zhang, Benjamin Bowen, Katherine Louie and 21 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
–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

83 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. EngineeringACS synthetic biology · 2026
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23 more citing papers are in PubMed but not listed here.

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

31 authors.

Gaoyan Wang *US Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Zhiying Zhao *US Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Jing Ke *US Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Yvonne Engel *Molecular Biotechnology, Department of Biosciences and Buchmann Institute for Molecular Life Sciences, Goethe Universität Frankfurt, Frankfurt am Main, Germany.
Yi-Ming Shi *Molecular Biotechnology, Department of Biosciences and Buchmann Institute for Molecular Life Sciences, Goethe Universität Frankfurt, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0001-6933-4971
David RobinsonUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Kerem BingolEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA.
Zheyun ZhangUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Benjamin BowenUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Katherine LouieUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Bing WangUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Robert EvansUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Yu MiyamotoUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Kelly ChengUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Suzanne KosinaEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-2885-1248
Markus De RaadEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-8263-9198
Leslie SilvaUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Alicia LuhrsEmery Pharma, Alameda, CA, USA.
Andrea LubbeEmery Pharma, Alameda, CA, USA.
David W HoytEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0002-2857-719X
Charles FrancavillaEmery Pharma, Alameda, CA, USA.
Hiroshi OtaniUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Samuel DeutschUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Nancy M WashtonEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA.
Edward M RubinUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.
Nigel J MounceyUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-5380-1256
Axel ViselUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-4130-7784
Trent NorthenUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-8404-3259
Jan-Fang ChengUS Department of Energy Joint Genome Institute, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-7315-7613
Helge B BodeUS Department of Energy Joint Genome Institute, Berkeley, CA, USA. h.bode@bio.uni-frankfurt.de.ORCID http://orcid.org/0000-0001-6048-5909
Yasuo YoshikuniUS Department of Energy Joint Genome Institute, Berkeley, CA, USA. yyoshikuni@lbl.gov.ORCID http://orcid.org/0000-0002-8372-640X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It is generally believed that exchange of secondary metabolite biosynthetic gene clusters (BGCs) among closely related bacteria is an important driver of BGC evolution and diversification. Applying this idea may help researchers efficiently connect many BGCs to their products and characterize the products' roles in various environments. However, existing genetic tools support only a small fraction of these efforts. Here, we present the development of chassis-independent recombinase-assisted genome engineering (CRAGE), which enables single-step integration of large, complex BGC constructs directly into the chromosomes of diverse bacteria with high accuracy and efficiency. To demonstrate the efficacy of CRAGE, we expressed three known and six previously identified but experimentally elusive non-ribosomal peptide synthetase (NRPS) and NRPS-polyketide synthase (PKS) hybrid BGCs from Photorhabdus luminescens in 25 diverse γ-Proteobacteria species. Successful activation of six BGCs identified 22 products for which diversity and yield were greater when the BGCs were expressed in strains closely related to the native strain than when they were expressed in either native or more distantly related strains. Activation of these BGCs demonstrates the feasibility of exploiting their underlying catalytic activity and plasticity, and provides evidence that systematic approaches based on CRAGE will be useful for discovering and identifying previously uncharacterized metabolites.

Indexed as

Multigene FamilyBacteriaBiosynthetic PathwaysGene Expression Regulation, BacterialGenes, BacterialGenetic EngineeringGenome, BacterialPeptide SynthasesPhotorhabdusPolyketide SynthasesRecombinasesSecondary Metabolismnon-ribosomal peptide synthasePeptide SynthasesPolyketide SynthasesRecombinases

Identifiers

What OpenQuestion holds

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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.