ArticleProceedings of the National Academy of Sciences of the United States of America2012
Fine-tuning gene networks using simple sequence repeats.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Automated characterization and analysis of expression compatibility between regulatory sequences and metabolic genes inSynthetic and systems biotechnology · 2024Article
- Transfer learning for cross-context prediction of protein expression from 5'UTR sequence.Nucleic acids research · 2024Article
- Utilizing 5' UTR Engineering Enables Fine-Tuning of Multiple Genes within Operons to Balance Metabolic Flux inBiology · 2024Article
- Using design of experiments to guide genetic optimization of engineered metabolic pathways.Journal of industrial microbiology & biotechnology · 2024Review
- Engineered multiple translation initiation sites: a novel tool to enhance protein production in Bacillus licheniformis and other industrially relevant bacteria.Nucleic acids research · 2022Article
- Bioindustrial manufacturing readiness levels (BioMRLs) as a shared framework for measuring and communicating the maturity of bioproduct manufacturing processes.Journal of industrial microbiology & biotechnology · 2022Article
- Independent control of mean and noise by convolution of gene expression distributions.Nature communications · 2021Article
- Context-Dependent Stability and Robustness of Genetic Toggle Switches with Leaky Promoters.Life (Basel, Switzerland) · 2021Article
- Biosensor-Based Multigene Pathway Optimization for Enhancing the Production of Glycolate.Applied and environmental microbiology · 2021Article
- Stability and Robustness of Unbalanced Genetic Toggle Switches in the Presence of Scarce Resources.Life (Basel, Switzerland) · 2021Article
- Construction of an Integrated mCherry Red Fluorescent Protein Expression System for Labeling and Tracing inFrontiers in microbiology · 2021Article
- Interaction variability shapes succession of synthetic microbial ecosystems.Nature communications · 2020Article
- Unraveling the Complex Interplay of Fis and IHF Through Synthetic Promoter Engineering.Frontiers in bioengineering and biotechnology · 2020Article
- Cell-free microcompartmentalised transcription-translation for the prototyping of synthetic communication networks.Current opinion in biotechnology · 2019Review
- Optogenetic control of Bacillus subtilis gene expression.Nature communications · 2019Article
- Diversity, versatility and complexity of bacterial gene regulation mechanisms: opportunities and drawbacks for applications in synthetic biology.FEMS microbiology reviews · 2019Review
- A novel riboregulator switch system of gene expression for enhanced microbial production of succinic acid.Journal of industrial microbiology & biotechnology · 2018Article
- Design of Adjacent Transcriptional Regions to Tune Gene Expression and Facilitate Circuit Construction.Cell systems · 2018Article
- A set of synthetic versatile genetic control elements for the efficient expression of genes in Actinobacteria.Scientific reports · 2018Article
- Mapping the operational landscape of microRNAs in synthetic gene circuits.NPJ systems biology and applications · 2018Article
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2 authors.
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Abstract
The parameters in a complex synthetic gene network must be extensively tuned before the network functions as designed. Here, we introduce a simple and general approach to rapidly tune gene networks in Escherichia coli using hypermutable simple sequence repeats embedded in the spacer region of the ribosome binding site. By varying repeat length, we generated expression libraries that incrementally and predictably sample gene expression levels over a 1,000-fold range. We demonstrate the utility of the approach by creating a bistable switch library that programmatically samples the expression space to balance the two states of the switch, and we illustrate the need for tuning by showing that the switch's behavior is sensitive to host context. Further, we show that mutation rates of the repeats are controllable in vivo for stability or for targeted mutagenesis--suggesting a new approach to optimizing gene networks via directed evolution. This tuning methodology should accelerate the process of engineering functionally complex gene networks.
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