Systems for in vivo hypermutation: a quest for scale and depth in directed evolution

Gordon Rix; Chang C Liu

doi:10.1016/j.cbpa.2021.02.008

Systems for in vivo hypermutation: a quest for scale and depth in directed evolution

Curr Opin Chem Biol. 2021 Oct:64:20-26. doi: 10.1016/j.cbpa.2021.02.008. Epub 2021 Mar 27.

Authors

Gordon Rix¹, Chang C Liu²

Affiliations

¹ Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA; Center for Synthetic Biology, The Henry Samueli School of Engineering, University of California, Irvine, CA, 92697, USA.
² Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA; Center for Synthetic Biology, The Henry Samueli School of Engineering, University of California, Irvine, CA, 92697, USA; Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA; Department of Chemistry, University of California, Irvine, CA, 92697, USA. Electronic address: ccl@uci.edu.

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.

Keywords: Continuous evolution; Directed evolution; Hypermutation; Protein evolution.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Directed Molecular Evolution
Evolution, Molecular*
Mutation
Proteins* / genetics

Substances

Proteins

Grants and funding

R35 GM136297/GM/NIGMS NIH HHS/United States