title: Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy.
abstract: Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A "P411" serine-ligated variant of cytochrome P450(BM3) has been engineered to initiate a sulfimidation/[2,3]-sigmatropic rearrangement sequence in whole E. coli cells, a non-natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non-allylic sulfides.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA, 91125, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Prier
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA, 91125, USA.
authors.forename: Todd K
authors.initials: TK
authors.lastname: Hyster
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA, 91125, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Farwell
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA, 91125, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Huang
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA, 91125, USA. frances@cheme.caltech.edu.
authors.forename: Frances H
authors.identifier: http://orcid.org/0000-0002-4027-364X
authors.initials: FH
authors.lastname: Arnold
mesh_terms: D000588:Amines / Q000138:chemical synthesis*; D004798:Enzymes / Q000737:chemistry*
chemical_list: D000588:Amines; D004798:Enzymes
keywords: amination; biocatalysis; cytochrome P450; directed evolution; nitrene transfer