Artificial Enzyme Design with an Abiological Salicylaldehyde Site Enables Biocatalytic Activation of Glycine Esters.

Here we describe the construction of an artificial enzyme bearing a biomimetic PLP-like catalytic center within an apo-myoglobin scaffold through covalent incorporation of an abiological salicylaldehyde moiety. By mimicking the substrate activation strategy employed by PLP-dependent enzymes, the engineered catalyst promotes the formation of reactive glycine ester nucleophiles and enables direct α-functionalization in C-C bond-forming reactions. This work establishes a biocatalytic platform for the synthesis of amino acid derivatives and illustrates how the integration of non-natural catalytic motifs into protein can unlock new-to-nature reactivity beyond the natural enzyme.