Systems for in vivo hypermutation: a quest for scale and depth in directed evolution |
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| Institution: | 1. Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA;2. Center for Synthetic Biology, The Henry Samueli School of Engineering, University of California, Irvine, CA, 92697, USA;3. Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA;4. Department of Chemistry, University of California, Irvine, CA, 92697, USA;1. Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA;2. BioTechnology Institute, University of Minnesota, St. Paul, MN, USA |
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| Abstract: | Traditional approaches to the directed evolution of genes of interest (GOIs) place constraints on the scale of experimentation and depth of evolutionary search reasonably achieved. Engineered genetic systems that dramatically elevate the mutation of target GOIs in vivo relieve these constraints by enabling continuous evolution, affording new strategies in the exploration of sequence space and fitness landscapes for GOIs. We describe various in vivo hypermutation systems for continuous evolution, discuss how different architectures for in vivo hypermutation facilitate evolutionary search scale and depth in their application to problems in protein evolution and engineering, and outline future opportunities for the field. |
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| Keywords: | Directed evolution Continuous evolution Protein evolution Hypermutation |
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