A Hydroxyquinoline‐Based Unnatural Amino Acid for the Design of Novel Artificial Metalloenzymes

We have examined the potential of the noncanonical amino acid (8‐hydroxyquinolin‐3‐yl)alanine (HQAla) for the design of artificial metalloenzymes. HQAla, a versatile chelator of late transition metals, was introduced into the lactococcal multidrug‐resistance regulator (LmrR) by stop codon suppression methodology. LmrR_HQAla was shown to complex efficiently with three different metal ions, Cu(II), Zn(II) and Rh(III) to form unique artificial metalloenzymes. The catalytic potential of the Cu(II)‐bound LmrR_HQAla enzyme was shown through its ability to catalyse asymmetric Friedel‐Craft alkylation and water addition, whereas the Zn(II)‐coupled enzyme was shown to mimic natural Zn hydrolase activity.