ArticleNature communications2020
Scalable continuous evolution for the generation of diverse enzyme variants encompassing promiscuous activities.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- Phage-assisted continuous evolution of enzymes for noncanonical tyrosine biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Harnessing the central dogma: Enzyme-driven gene diversification strategies for in cellulo continuous directed evolution.Fundamental research · 2026Review
- Humanized Anti-PD-1 Antibodies Generated Using The Conditional Kernel-Elastic Autoencoder.bioRxiv : the preprint server for biology · 2026Article
- Replication-coupled dual-deaminase mutagenesis (RCDM) enables continuous genomic evolution in Bacillus subtilis.Microbial cell factories · 2026Article
- Phage-assisted continuous evolution of enzymes for noncanonical tyrosine biosynthesis.bioRxiv : the preprint server for biology · 2026Article
- Harnessing Nature's Algorithm: From Test Tubes to Autonomous In Vivo Evolution.Biotechnology journal · 2026Review
- Highly mutagenic continuous evolution in E. coli using a Φ29-based orthogonal replication system.Nature biotechnology · 2026Article
- Continuous Hypermutation and Evolution of Luciferase Variants.ACS chemical biology · 2026Article
- Sequence-based generative AI design of versatile tryptophan synthases.Nature communications · 2026Article
- Knowledgeable Language Models as Black-Box Optimizers for Personalized Medicine.... International Conference on Learning Representations · 2026Article
- Dissecting the disconnect between circuit activation and dominant adaptive evolution in cytoplasmic phage-assisted continuous evolution (PACE) of an EGFR nanobody.Frontiers in bioengineering and biotechnology · 2026Article
- Glycoengineering strategies for constructing defined Mucin O-glycans.Frontiers in molecular biosciences · 2026Review
- Orthogonal replication with optogenetic selection evolves yeast JEN1 into a mevalonate transporter.Molecular systems biology · 2025Article
- Considering Metabolic Context in Enzyme Evolution and Design.Biochemistry · 2025Review
- Directed evolution of aminoacyl-tRNA synthetases through in vivo hypermutation.Nature communications · 2025Article
- Ultra-efficient Integration of Gene Libraries onto Yeast Cytosolic Plasmids.ACS synthetic biology · 2025Article
- Recent advances in targeted mutagenesis to expedite the evolution of biological systems.Journal of microbiology (Seoul, Korea) · 2025Review
- Directed Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System.ACS catalysis · 2025Article
- Accelerated enzyme engineering by machine-learning guided cell-free expression.Nature communications · 2025Article
- Bioengineering hybrid artificial life.Frontiers in bioinformatics · 2025Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Enzyme orthologs sharing identical primary functions can have different promiscuous activities. While it is possible to mine this natural diversity to obtain useful biocatalysts, generating comparably rich ortholog diversity is difficult, as it is the product of deep evolutionary processes occurring in a multitude of separate species and populations. Here, we take a first step in recapitulating the depth and scale of natural ortholog evolution on laboratory timescales. Using a continuous directed evolution platform called OrthoRep, we rapidly evolve the Thermotoga maritima tryptophan synthase β-subunit (TmTrpB) through multi-mutation pathways in many independent replicates, selecting only on TmTrpB's primary activity of synthesizing L-tryptophan from indole and L-serine. We find that the resulting sequence-diverse TmTrpB variants span a range of substrate profiles useful in industrial biocatalysis and suggest that the depth and scale of evolution that OrthoRep affords will be generally valuable in enzyme engineering and the evolution of biomolecular functions.
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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.