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

一种基于羟基喹啉的非天然氨基酸用于设计新型人工金属酶

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Abstract

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.

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