ArticleMolecular systems biology2014
Efficient search, mapping, and optimization of multi-protein genetic systems in diverse bacteria.
Article in Molecular systems biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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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.
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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.
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Who cites it
95 citing papers in PubMed, 234 citations in OpenAlex.
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- Cellulase secretion by engineered Pseudomonas putida enables growth on cellulose oligomers.Applied microbiology and biotechnology · 2025Article
- Unraveling the start element and regulatory divergence of core promoters across the domain bacteria.Nucleic acids research · 2025Article
- Reusable combinatorial libraries with high diversity for efficient multi-gene expression optimization in Escherichia coli.World journal of microbiology & biotechnology · 2025Article
- One-carbon fixation via the synthetic reductive glycine pathway exceeds yield of the Calvin cycle.Nature microbiology · 2025Article
- Construction and Application of a Multienzyme System for Synthesis of L-malate.Applied biochemistry and biotechnology · 2024Article
- Building Synthetic Cells─From the Technology Infrastructure to Cellular Entities.ACS synthetic biology · 2024Review
- Development of modular expression across phylogenetically distinct diazotrophs.Journal of industrial microbiology & biotechnology · 2024Article
- Selective and Site-Specific Incorporation of Nonstandard Amino Acids Within Proteins for Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Accelerating Genetic Sensor Development, Scale-up, and Deployment Using Synthetic Biology.Biodesign research · 2024Article
- Research and application of intelligent diagnosis and treatment engineering bacteria.Frontiers in bioengineering and biotechnology · 2024Review
- A potential paradigm in CRISPR/Cas systems delivery: at the crossroad of microalgal gene editing and algal-mediated nanoparticles.Journal of nanobiotechnology · 2023Review
- Next generation synthetic memory via intercepting recombinase function.Nature communications · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Developing predictive models of multi-protein genetic systems to understand and optimize their behavior remains a combinatorial challenge, particularly when measurement throughput is limited. We developed a computational approach to build predictive models and identify optimal sequences and expression levels, while circumventing combinatorial explosion. Maximally informative genetic system variants were first designed by the RBS Library Calculator, an algorithm to design sequences for efficiently searching a multi-protein expression space across a > 10,000-fold range with tailored search parameters and well-predicted translation rates. We validated the algorithm's predictions by characterizing 646 genetic system variants, encoded in plasmids and genomes, expressed in six gram-positive and gram-negative bacterial hosts. We then combined the search algorithm with system-level kinetic modeling, requiring the construction and characterization of 73 variants to build a sequence-expression-activity map (SEAMAP) for a biosynthesis pathway. Using model predictions, we designed and characterized 47 additional pathway variants to navigate its activity space, find optimal expression regions with desired activity response curves, and relieve rate-limiting steps in metabolism. Creating sequence-expression-activity maps accelerates the optimization of many protein systems and allows previous measurements to quantitatively inform future designs.
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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.