ArticleJournal of molecular evolution2011
Exploiting models of molecular evolution to efficiently direct protein engineering.
Article in Journal of molecular evolution, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Biosensor-guided directed evolution of aldehyde dehydrogenase for improved adipic acid production from caprolactone.Journal of biological engineering · 2026Article
- Engineering of Nocardioides acrostichi lipase: utilizing natural variation and mutational free energy to alter expression and functional properties.Journal of biological engineering · 2025Article
- Ancestral Protein-Based Lighting.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Engineering Substrate Promiscuity of Nucleoside Phosphorylase Via an Insertions-Deletions Strategy.JACS Au · 2024Article
- Thermophilic Nucleic Acid Polymerases and Their Application in Xenobiology.International journal of molecular sciences · 2022Review
- Engineering functional thermostable proteins using ancestral sequence reconstruction.The Journal of biological chemistry · 2022Review
- HyperXpress: Rapid Single Vessel DNA Assembly and Protein Production in Microliterscale.Frontiers in bioengineering and biotechnology · 2022Article
- Heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase.Nature communications · 2021Article
- Enzyme-mediated depletion of serum l-Met abrogates prostate cancer growth via multiple mechanisms without evidence of systemic toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Incorporation of Modified Amino Acids by Engineered Elongation Factors with Expanded Substrate Capabilities.ACS synthetic biology · 2019Article
- Ancestral protein resurrection and engineering opportunities of the mamba aminergic toxins.Scientific reports · 2017Article
- Effects of point mutations on the thermostability of B. subtilis lipase: investigating nonadditivity.Journal of computer-aided molecular design · 2016Article
- An experimental phylogeny to benchmark ancestral sequence reconstruction.Nature communications · 2016Article
- The Toolbox for Modified Aptamers.Molecular biotechnology · 2016Review
- Suppression Subtractive Hybridization Versus Next-Generation Sequencing in Plant Genetic Engineering: Challenges and Perspectives.Molecular biotechnology · 2015Review
- The functional importance of co-evolving residues in proteins.Cellular and molecular life sciences : CMLS · 2014Review
- DNA polymerases engineered by directed evolution to incorporate non-standard nucleotides.Frontiers in microbiology · 2014Review
- Interchanging functionality among homologous elongation factors using signatures of heterotachy.Journal of molecular evolution · 2013Article
- Bacterial and fungal chitinase chiJ orthologs evolve under different selective constraints following horizontal gene transfer.BMC research notes · 2012Article
- Directed evolution: an evolving and enabling synthetic biology tool.Current opinion in chemical biology · 2012Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Directed evolution and protein engineering approaches used to generate novel or enhanced biomolecular function often use the evolutionary sequence diversity of protein homologs to rationally guide library design. To fully capture this sequence diversity, however, libraries containing millions of variants are often necessary. Screening libraries of this size is often undesirable due to inaccuracies of high-throughput assays, costs, and time constraints. The ability to effectively cull sequence diversity while still generating the functional diversity within a library thus holds considerable value. This is particularly relevant when high-throughput assays are not amenable to select/screen for certain biomolecular properties. Here, we summarize our recent attempts to develop an evolution-guided approach, Reconstructing Evolutionary Adaptive Paths (REAP), for directed evolution and protein engineering that exploits phylogenetic and sequence analyses to identify amino acid substitutions that are likely to alter or enhance function of a protein. To demonstrate the utility of this technique, we highlight our previous work with DNA polymerases in which a REAP-designed small library was used to identify a DNA polymerase capable of accepting non-standard nucleosides. We anticipate that the REAP approach will be used in the future to facilitate the engineering of biopolymers with expanded functions and will thus have a significant impact on the developing field of 'evolutionary synthetic biology'.
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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.