ArticleACS synthetic biology2019
GeneORator: An Effective Strategy for Navigating Protein Sequence Space More Efficiently through Boolean OR-Type DNA Libraries.
Article in ACS synthetic biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Engineering selective amyloid precursor protein inhibitors by machine learning and deep mutational scanning.Protein science : a publication of the Protein Society · 2026Article
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Deep neural networks for predicting the affinity landscape of protein-protein interactions.iScience · 2024Article
- SpeedyGenesXL: an Automated, High-Throughput Platform for the Preparation of Bespoke Ultralarge Variant Libraries for Directed Evolution.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Directed Evolution of Transcription Factor-Based Biosensors for Altered Effector Specificity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A palette of fluorophores that are differentially accumulated by wild-type and mutant strains ofMicrobiology (Reading, England) · 2021Article
- Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020Review
- Enhancing aChemical science · 2020Article
- The evolving art of creating genetic diversity: From directed evolution to synthetic biology.Biotechnology advancesReview
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Authors and funding
9 authors.
Funding
Abstract
Directed evolution requires the creation of genetic diversity and subsequent screening or selection for improved variants. For DNA mutagenesis, conventional site-directed methods implicitly utilize the Boolean AND operator (creating all mutations simultaneously), producing a combinatorial explosion in the number of genetic variants as the number of mutations increases. We introduce GeneORator, a novel strategy for creating DNA libraries based on the Boolean logical OR operator. Here, a single library is divided into many subsets, each containing different combinations of the desired mutations. Consequently, the effect of adding more mutations on the number of genetic combinations is additive (Boolean OR logic) and not exponential (AND logic). We demonstrate this strategy with large-scale mutagenesis studies, using monoamine oxidase-N ( Aspergillus niger) as the exemplar target. First, we mutated every residue in the secondary structure-containing regions (276 out of a total 495 amino acids) to screen for improvements in k
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