ArticleNature communications2022
Integrase-mediated differentiation circuits improve evolutionary stability of burdensome and toxic functions in E. coli.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- A Proposed Cross-Feeding Model of Phenanthrene Degradation by Constructed Halophilic Consortium NOMA.Microorganisms · 2026Article
- Cascading recombinase memory switch for programmable and stable gene expression in Pseudomonas putida.Nucleic acids research · 2026Article
- Tunable low-rate genomic recombination with Cre-Applied and environmental microbiology · 2026Article
- Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Exploring the computing power of microbes that shapes the environment.Current opinion in microbiology · 2026Review
- Programmable cell differentiation in budding yeast uncouples reproductive and metabolic tasks.bioRxiv : the preprint server for biology · 2025Article
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- Why cellular computations challenge our design principles.Seminars in cell & developmental biology · 2025Review
- The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025Review
- Preventing Multimer Formation in Commonly Used Synthetic Biology Plasmids.ACS synthetic biology · 2025Article
- Model-guided gene circuit design for engineering genetically stable cell populations in diverse applications.Journal of the Royal Society, Interface · 2025Article
- Tuning and functionalization of logic gates for time resolved programming of bacterial populations.Nucleic acids research · 2025Article
- Harnessing microbial heterogeneity for improved biosynthesis fueled by synthetic biology.Synthetic and systems biotechnology · 2025Review
- Article
- Customizing cellular signal processing by synthetic multi-level regulatory circuits.Nature communications · 2023Review
- Prolonging genetic circuit stability through adaptive evolution of overlapping genes.Nucleic acids research · 2023Article
- Addressable and adaptable intercellular communication via DNA messaging.Nature communications · 2023Article
- Integrase-mediated differentiation circuits improve evolutionary stability of burdensome and toxic functions in E. coli.Nature communications · 2022Article
- Dynamic cybergenetic control of bacterial co-culture composition via optogenetic feedback.Nature communications · 2022Article
Corrections and comments
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2 authors.
Funding
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Abstract
Advances in synthetic biology, bioengineering, and computation allow us to rapidly and reliably program cells with increasingly complex and useful functions. However, because the functions we engineer cells to perform are typically burdensome to cell growth, they can be rapidly lost due to the processes of mutation and natural selection. Here, we show that a strategy of terminal differentiation improves the evolutionary stability of burdensome functions in a general manner by realizing a reproductive and metabolic division of labor. To implement this strategy, we develop a genetic differentiation circuit in Escherichia coli using unidirectional integrase-recombination. With terminal differentiation, differentiated cells uniquely express burdensome functions driven by the orthogonal T7 RNA polymerase, but their capacity to proliferate is limited to prevent the propagation of advantageous loss-of-function mutations that inevitably occur. We demonstrate computationally and experimentally that terminal differentiation increases duration and yield of high-burden expression and that its evolutionary stability can be improved with strategic redundancy. Further, we show this strategy can even be applied to toxic functions. Overall, this study provides an effective, generalizable approach for protecting burdensome engineered functions from evolutionary degradation.
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