A Hydroxyquinoline‐Based Unnatural Amino Acid for the Design of Novel Artificial Metalloenzymes
ChemBioChem 2020, 21, 3077-3081, 10.1002/cbic.202000306
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, CuII, ZnII and RhIII to form unique artificial metalloenzymes. The catalytic potential of the CuII-bound LmrR_HQAla enzyme was shown through its ability to catalyse asymmetric Friedel-Craft alkylation and water addition, whereas the ZnII-coupled enzyme was shown to mimic natural Zn hydrolase activity.
Metal: CuReaction: Friedel-Crafts alkylationMax TON: 11ee: 51Notes: Also used Rh, but no reaction detected.
Metal: CuReaction: Water additionMax TON: ---ee: ---Notes: ---
Metal: ZnReaction: C-H activationMax TON: ---ee: ---Notes: ---