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

Ivana Drienovská; Remkes A Scheele; Cora Gutiérrez de Souza; Gerard Roelfes

doi:10.1002/cbic.202000306

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

Ivana Drienovská, Remkes A Scheele, Cora Gutiérrez de Souza, Gerard Roelfes^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3077-3081
Number of pages	6
Journal	ChemBioChem
Issue number	21
DOIs	https://doi.org/10.1002/cbic.202000306
Publication status	E-pub ahead of print - 25-Jun-2020

Keywords

biocatalysis
hybrid catalysts
metalloenzymes
noncanonical amino acids
protein design
GENETIC INCORPORATION
COMPUTATIONAL DESIGN
TERMINAL ALKYNES
PROTEIN
COMPLEXES
BINDING
DERIVATIVES
8-HYDROXYQUINOLINE
METALLOPROTEIN
SITES

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A hydroxyquinoline-based unnatural amino acid for the design of novel artificial metalloenzymes
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@article{7aebf21b2f544e6094324d20e770a88c,

title = "A Hydroxyquinoline-Based Unnatural Amino Acid for the Design of Novel Artificial Metalloenzymes",

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.",

keywords = "biocatalysis, hybrid catalysts, metalloenzymes, noncanonical amino acids, protein design, GENETIC INCORPORATION, COMPUTATIONAL DESIGN, TERMINAL ALKYNES, PROTEIN, COMPLEXES, BINDING, DERIVATIVES, 8-HYDROXYQUINOLINE, METALLOPROTEIN, SITES",

author = "Ivana Drienovsk{\'a} and Scheele, {Remkes A} and {de Souza}, {Cora Guti{\'e}rrez} and Gerard Roelfes",

note = "{\textcopyright} 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2020",

month = jun,

day = "25",

doi = "10.1002/cbic.202000306",

language = "English",

pages = "3077--3081",

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T1 - A Hydroxyquinoline-Based Unnatural Amino Acid for the Design of Novel Artificial Metalloenzymes

AU - Drienovská, Ivana

AU - Scheele, Remkes A

AU - de Souza, Cora Gutiérrez

AU - Roelfes, Gerard

PY - 2020/6/25

Y1 - 2020/6/25

N2 - 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.

AB - 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.

KW - biocatalysis

KW - hybrid catalysts

KW - metalloenzymes

KW - noncanonical amino acids

KW - protein design

KW - GENETIC INCORPORATION

KW - COMPUTATIONAL DESIGN

KW - TERMINAL ALKYNES

KW - PROTEIN

KW - COMPLEXES

KW - BINDING

KW - DERIVATIVES

KW - 8-HYDROXYQUINOLINE

KW - METALLOPROTEIN

KW - SITES

U2 - 10.1002/cbic.202000306

DO - 10.1002/cbic.202000306

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JO - ChemBioChem

JF - ChemBioChem

SN - 1439-4227

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