Engineering MDR-based artificial enzymes

Natural enzymes are sustainable catalysts, but their limited reaction range restricts their use. This thesis explores artificial enzymes designed for non-natural, synthetically valuable transformations. Multidrug resistance regulators served as scaffolds, modified by stop codon suppression to incorporate unnatural amino acids with synthetic catalytic groups. The resulting enzymes were evaluated for activity, selectivity, and evolvability. In particular, LmrR containing para-aminophenylalanine (LmrR_pAF) enabled intramolecular Friedel–Crafts alkylation to synthesize tetrahydrocarbazoles, with an unstable aldehyde intermediate generated in situ via a one-pot cascade with the natural oxidase HMFO.