ArticleNucleic acids research2023
Prolonging genetic circuit stability through adaptive evolution of overlapping genes.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
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- Generative design of synthetic gene circuits for functional and evolutionary properties.NPJ systems biology and applications · 2026Article
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- Genetically Modified Microorganisms: Risks and Regulatory Considerations for Human and Environmental Health.Microorganisms · 2026Review
- SUPER: Upcycling Genetic Parts for Precise Gene Expression Control, Leakage Minimization, and Genetic Circuit Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tuning evolvability via plasmid copy number and regulatory architecture.Nature communications · 2025Article
- Advanced adhesion and targeting strategies to prolong gut residence time and improve eLBP efficacy in colonic diseases.Advanced drug delivery reviews · 2025Review
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- Genetic controllers for enhancing the evolutionary longevity of synthetic gene circuits in bacteria.Nature communications · 2025Article
- Genetic Entanglement Enables Ultrastable Biocontainment in the Mammalian Gut.ACS synthetic biology · 2025Article
- Secure biosystems design inApplied and environmental microbiology · 2025Article
- A framework for challenges and solutions in biodesign research.Biodesign research · 2025Article
- Design of overlapping genes using deep generative models of protein sequences.bioRxiv : the preprint server for biology · 2025Article
- The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025Review
- Identification and monitoring of cell heterogeneity from plasmid recombination during limonene production.Applied microbiology and biotechnology · 2025Article
- Genetically modified microorganisms for agricultural use: an opportunity for the advancement of risk assessment criteria in Argentina.Frontiers in bioengineering and biotechnology · 2025Article
- Synthetic biology approaches to enhance cancer immune responses.Frontiers in immunology · 2025Review
- Toxin-Antitoxin Systems Reflect Community Interactions Through Horizontal Gene Transfer.Molecular biology and evolution · 2024Article
- Degradation of polyethylene terephthalate (PET) plastics by wastewater bacteria engineered via conjugation.Microbial biotechnology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of synthetic biological circuits that maintain functionality over application-relevant time scales remains a significant challenge. Here, we employed synthetic overlapping sequences in which one gene is encoded or 'entangled' entirely within an alternative reading frame of another gene. In this design, the toxin-encoding relE was entangled within ilvA, which encodes threonine deaminase, an enzyme essential for isoleucine biosynthesis. A functional entanglement construct was obtained upon modification of the ribosome-binding site of the internal relE gene. Using this optimized design, we found that the selection pressure to maintain functional IlvA stabilized the production of burdensome RelE for >130 generations, which compares favorably with the most stable kill-switch circuits developed to date. This stabilizing effect was achieved through a complete alteration of the allowable landscape of mutations such that mutations inactivating the entangled genes were disfavored. Instead, the majority of lineages accumulated mutations within the regulatory region of ilvA. By reducing baseline relE expression, these more 'benign' mutations lowered circuit burden, which suppressed the accumulation of relE-inactivating mutations, thereby prolonging kill-switch function. Overall, this work demonstrates the utility of sequence entanglement paired with an adaptive laboratory evolution campaign to increase the evolutionary stability of burdensome synthetic circuits.
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Registered trials
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.