Issue 14, 2017

Multidrug resistance regulators (MDRs) as scaffolds for the design of artificial metalloenzymes

Abstract

The choice of protein scaffolds is an important element in the design of artificial metalloenzymes. Herein, we introduce Multidrug Resistance Regulators (MDRs) from the TetR family as a viable class of protein scaffolds for artificial metalloenzyme design. In vivo incorporation of the metal binding amino acid (2,2-bipyridin-5yl)alanine (BpyA) by stop codon suppression methods was used to create artificial metalloenzymes from three members of the TetR family of MDRs: QacR, CgmR and RamR. Excellent results were achieved with QacR Y123BpyA in the Cu2+ catalyzed enantioselective vinylogous Friedel–Crafts alkylation reaction with ee's up to 94% of the opposite enantiomer that was achieved with other mutants and the previously reported LmrR-based artificial metalloenzymes.

Graphical abstract: Multidrug resistance regulators (MDRs) as scaffolds for the design of artificial metalloenzymes

Supplementary files

Article information

Article type
Paper
Submitted
16 2月 2017
Accepted
14 3月 2017
First published
14 3月 2017

Org. Biomol. Chem., 2017,15, 3069-3073

Multidrug resistance regulators (MDRs) as scaffolds for the design of artificial metalloenzymes

M. Bersellini and G. Roelfes, Org. Biomol. Chem., 2017, 15, 3069 DOI: 10.1039/C7OB00390K

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