ArticleACS synthetic biology2018
Orthogonality and Burdens of Heterologous AND Gate Gene Circuits in E. coli.
Article in ACS synthetic biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Expanding salivary biomarker detection by creating a synthetic neuraminic acid sensor via chimeragenesis.Applied and environmental microbiology · 2026Article
- Multiplexed CRISPR base editing enables pulse-activated irreversible biocontainment of engineered bacteria.Nucleic acids research · 2026Article
- Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Programming RNA Trans-Splicing for Versatile Gene Regulation and Complex Cellular Logic Computation.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Biosensors for Cancer and Inflammation: Whole-Cell Biosensors for Soluble Molecules.Methods in molecular biology (Clifton, N.J.) · 2026Article
- 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
- Partitioning of a 2-bit hash function across 66 communicating cells.Nature chemical biology · 2025Article
- Biosensor characterization: formal methods from the perspective of proteome fractions.Synthetic biology (Oxford, England) · 2025Article
- Bacterial microcompartment utilization in the human commensalJournal of bacteriology · 2024Article
- Laccase is a multitasking protein for synthetic gene circuits in the yeastSynthetic and systems biotechnology · 2024Article
- Probing the orthogonality and robustness of the mammalian RNA-binding protein Musashi-1 in Escherichia coli.Journal of biological engineering · 2024Article
- Data-driven learning of structure augments quantitative prediction of biological responses.PLoS computational biology · 2024Article
- Toward predictable universal genetic circuit design.Quantitative biology (Beijing, China) · 2024Article
- Engineering intelligent chassis cells via recombinase-based MEMORY circuits.Nature communications · 2024Article
- Evaluating the feasibility of medium-chain oleochemical synthesis using microbial chain elongation.Journal of industrial microbiology & biotechnology · 2024Article
- Accelerating Genetic Sensor Development, Scale-up, and Deployment Using Synthetic Biology.Biodesign research · 2024Article
- GenoMine: a CRISPR-Cas9-based kill switch for biocontainment ofFrontiers in bioengineering and biotechnology · 2024Article
- Customizing cellular signal processing by synthetic multi-level regulatory circuits.Nature communications · 2023Review
- Impact of mixing insufficiencies on L-phenylalanine production with an Escherichia coli reporter strain in a novel two-compartment bioreactor.Microbial cell factories · 2023Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Synthetic biology approaches commonly introduce heterologous gene networks into a host to predictably program cells, with the expectation of the synthetic network being orthogonal to the host background. However, introduced circuits may interfere with the host's physiology, either indirectly by posing a metabolic burden and/or through unintended direct interactions between parts of the circuit with those of the host, affecting functionality. Here we used RNA-Seq transcriptome analysis to quantify the interactions between a representative heterologous AND gate circuit and the host Escherichia coli under various conditions including circuit designs and plasmid copy numbers. We show that the circuit plasmid copy number outweighs circuit composition for their effect on host gene expression with medium-copy number plasmid showing more prominent interference than its low-copy number counterpart. In contrast, the circuits have a stronger influence on the host growth with a metabolic load increasing with the copy number of the circuits. Notably, we show that variation of copy number, an increase from low to medium copy, caused different types of change observed in the behavior of components in the AND gate circuit leading to the unbalance of the two gate-inputs and thus counterintuitive output attenuation. The study demonstrates the circuit plasmid copy number is a key factor that can dramatically affect the orthogonality, burden and functionality of the heterologous circuits in the host chassis. The results provide important guidance for future efforts to design orthogonal and robust gene circuits with minimal unwanted interaction and burden to their host.
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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.