Evidence map›Paper›PMID 33850130›Full record

ArticleNature communications2021

A systematic approach to inserting split inteins for Boolean logic gate engineering and basal activity reduction.

Trevor Y H Ho, Alexander Shao, Zeyu Lu, Harri Savilahti, Filippo Menolascina, Lei Wang, Neil Dalchau, Baojun Wang

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Why cellular computations challenge our design principles.Seminars in cell & developmental biology · 2025
    Review
  7. Article
  8. Frontiers in bioengineering and biotechnology · 2025
    Article
  9. Review
  10. Toward predictable universal genetic circuit design.Quantitative biology (Beijing, China) · 2024
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Noise logic with an InGaN/SiNScientific reports · 2022
    Article
  18. Efficient gene editing through an intronic selection marker in cells.Cellular and molecular life sciences : CMLS · 2022
    Article
  19. Protein Splicing of Inteins: A Powerful Tool in Synthetic Biology.Frontiers in bioengineering and biotechnology · 2022
    Review
  20. 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

8 authors.

Trevor Y H HoCentre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.ORCID 0000-0003-2969-0677
Alexander ShaoCentre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
Zeyu LuCentre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.ORCID 0000-0001-6536-6407
Harri SavilahtiDepartment of Biology, University of Turku, Turku, Finland.
Filippo MenolascinaInstitute for Bioengineering, School of Engineering, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-4937-7912
Lei WangSchool of Engineering, Westlake University, Hangzhou, China.
Neil DalchauMicrosoft Research, Cambridge, UK.ORCID 0000-0002-4872-6914
Baojun WangCentre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK. baojun.wang@ed.ac.uk.ORCID 0000-0002-4858-8937

Funding

Biotechnology and Biological Sciences Research Council BB/N007212/1Medical Research Council MR/S018875/1
6 · The paper itself

Abstract

Split inteins are powerful tools for seamless ligation of synthetic split proteins. Yet, their use remains limited because the already intricate split site identification problem is often complicated by the requirement of extein junction sequences. To address this, we augment a mini-Mu transposon-based screening approach and devise the intein-assisted bisection mapping (IBM) method. IBM robustly reveals clusters of split sites on five proteins, converting them into AND or NAND logic gates. We further show that the use of inteins expands functional sequence space for splitting a protein. We also demonstrate the utility of our approach over rational inference of split sites from secondary structure alignment of homologous proteins, and that basal activities of highly active proteins can be mitigated by splitting them. Our work offers a generalizable and systematic route towards creating split protein-intein fusions for synthetic biology.

Indexed as

Escherichia coliEscherichia coli ProteinsHigh-Throughput Nucleotide SequencingInteinsModels, MolecularProtein ConformationProtein EngineeringProteinsProtein SplicingSynthetic BiologyEscherichia coli ProteinsProteins

Identifiers

PMID33850130
PMCPMC8044194

What OpenQuestion holds

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LicenceCC BY
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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.