title: Optimizing non-natural protein function with directed evolution.
abstract: Developing technologies such as unnatural amino acid mutagenesis, non-natural cofactor engineering, and computational design are generating proteins with novel functions; these proteins, however, often do not reach performance targets and would benefit from further optimization. Evolutionary methods can complement these approaches: recent work combining unnatural amino acid mutagenesis and phage selection has created useful proteins of novel composition. Weak initial activity in a computationally designed enzyme has been improved by iterative rounds of mutagenesis and screening. A marriage of ingenuity and evolution will expand the scope of protein function well beyond Mother Nature's designs.
authors.affiliation: Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brustad
authors.forename: Frances H
authors.initials: FH
authors.lastname: Arnold
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000235:genetics; D000818:Animals; D019020:Directed Molecular Evolution / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D015202:Protein Engineering / Q000379:methods*; D011506:Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D000596:Amino Acids; D011506:Proteins