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

AIMMS

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

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	5
Journal	ChemBioChem
Volume	21
Issue number	21
Early online date	25 Jun 2020
DOIs	https://doi.org/10.1002/cbic.202000306
Publication status	Published - 2 Nov 2020

Funding

This work was supported by the Netherlands Organization for Scientific Research (NWO, vici grant 724.013.003) and the European Research Council (ERC starting grant 280010). GR acknowledges support from the Netherlands Ministry of Education, Culture and Science (Gravitation program no. 024.001.035). The authors thank Prof. P. G. Schultz (The Scripps Research Institute, USA) for kindly providing the pEVOL_HQAla plasmid and Ruben Maaskant for useful suggestions and discussion regarding the synthesis of HQAla.

Funders	Funder number
Scripps Research Institute
European Commission
European Research Council
Ministerie van Onderwijs, Cultuur en Wetenschap
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	724.013.003, 024.001.035
Seventh Framework Programme	280010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 6 Clean Water and Sanitation

Keywords

biocatalysis
hybrid catalysts
metalloenzymes
noncanonical amino acids
protein design

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10.1002/cbic.202000306

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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, 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.",

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AU - Drienovská, Ivana

AU - Scheele, Remkes A.

AU - Gutiérrez de Souza, Cora

AU - Roelfes, Gerard

PY - 2020/11/2

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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, 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.

KW - biocatalysis

KW - hybrid catalysts

KW - metalloenzymes

KW - noncanonical amino acids

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

Abstract

Funding

UN SDGs

Keywords

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