Unlocking Iminium Catalysis in Artificial Enzymes to Create a Friedel-Crafts Alkylase.

ABSTRACT: The construction and engineering of artificial enzymes consisting of abiological catalytic moieties incorporated into protein scaffolds is a promising strategy to realize non-natural mechanisms in biocatalysis. Here, we show that incorporation of the noncanonical amino acid para-aminophenylalanine (pAF) into the nonenzymatic protein scaffold LmrR creates a proficient and stereoselective artificial enzyme (LmrR_pAF) for the vinylogous Friedel-Crafts alkylation between α,β-unsaturated aldehydes and indoles. pAF acts as a catalytic residue, activating enal substrates toward conjugate addition via the formation of intermediate iminium ion species, while the protein scaffold provides rate acceleration and stereoinduction. Improved LmrR_pAF variants were identified by low-throughput directed evo

SUBMITTER: Leveson-Gower RB 

PROVIDER: S-EPMC8218303 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature