Evidence map›Paper›PMID 29789543›Full record

ArticleNature communications2018

Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods.

Wei Liu, Zhouqing Luo, Yun Wang, Nhan T Pham, Laura Tuck, Irene Pérez-Pi, Longying Liu, Yue Shen, Chris French, Manfred Auer and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing 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

72 citing papers in PubMed.

  1. Article
  2. Review
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  5. Review
  6. Article
  7. Article
  8. Gene circuit-based sensors.Fundamental research · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Golden Gate Cloning for Efficient Biosynthesis of Lycopene in Synthetic Yeast.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  17. Review
  18. Review
  19. Article
  20. Article

12 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

13 authors.

Wei LiuSchool of Biological Sciences, The King's Buildings, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Zhouqing LuoCenter for Synthetic Genomics, Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China.
Yun WangBGI-Shenzhen, Beishan Industrial Zone, 518083, Shenzhen, China.
Nhan T PhamSchool of Biological Sciences, The King's Buildings, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Laura TuckSchool of Biological Sciences, The King's Buildings, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Irene Pérez-PiSchool of Biological Sciences, The King's Buildings, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Longying LiuBGI-Shenzhen, Beishan Industrial Zone, 518083, Shenzhen, China.
Yue ShenSchool of Biological Sciences, The King's Buildings, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Chris FrenchSchool of Biological Sciences, The King's Buildings, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Manfred AuerSchool of Biological Sciences, The King's Buildings, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Jon Marles-WrightSchool of Natural and Environmental Sciences, Devonshire Building, Newcastle University, Newcastle upon, Tyne, NE1 7RX, UK.ORCID http://orcid.org/0000-0002-9156-3284
Junbiao DaiCenter for Synthetic Genomics, Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China. junbiao.dai@siat.ac.cn.ORCID http://orcid.org/0000-0002-5299-4700
Yizhi CaiCenter for Synthetic Genomics, Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China. yizhi.cai@manchester.ac.uk.ORCID http://orcid.org/0000-0003-1663-2865

Funding

Biotechnology and Biological Sciences Research Council BB/M005690/1Biotechnology and Biological Sciences Research Council BB/M017702/1Biotechnology and Biological Sciences Research Council BB/M025640/1Wellcome Trust
6 · The paper itself

Abstract

Exogenous pathway optimization and chassis engineering are two crucial methods for heterologous pathway expression. The two methods are normally carried out step-wise and in a trial-and-error manner. Here we report a recombinase-based combinatorial method (termed "SCRaMbLE-in") to tackle both challenges simultaneously. SCRaMbLE-in includes an in vitro recombinase toolkit to rapidly prototype and diversify gene expression at the pathway level and an in vivo genome reshuffling system to integrate assembled pathways into the synthetic yeast genome while combinatorially causing massive genome rearrangements in the host chassis. A set of loxP mutant pairs was identified to maximize the efficiency of the in vitro diversification. Exemplar pathways of β-carotene and violacein were successfully assembled, diversified, and integrated using this SCRaMbLE-in method. High-throughput sequencing was performed on selected engineered strains to reveal the resulting genotype-to-phenotype relationships. The SCRaMbLE-in method proves to be a rapid, efficient, and universal method to fast track the cycle of engineering biology.

Indexed as

Gene Expression Regulation, FungalGenes, SyntheticGenome, FungalBase Sequencebeta CaroteneChromosomes, FungalGenetic Association StudiesGenetic EngineeringGenotypeHigh-Throughput Nucleotide SequencingIndolesIntegrasesMetabolic Networks and PathwaysPhenotypePlasmidsRecombination, Geneticbeta CaroteneCre recombinaseIndolesIntegrasesviolacein

Identifiers

PMID29789543
PMCPMC5964202

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.