A Hydroxyquinoline‐Based Unnatural Amino Acid for the Design of Novel Artificial Metalloenzymes. (17th July 2020)

• Record Type: Journal Article
• Authors: Drienovská, Ivana; Scheele, Remkes A.; Gutiérrez de Souza, Cora; Roelfes, Gerard
• Is Part Of: Chembiochem. Volume 21:Number 21(2020)
• Page Start: 3077
• Page End: 3081
• Publication Date: 2020-07-17
• Subjects: biocatalysis -- hybrid catalysts -- metalloenzymes -- noncanonical amino acids -- protein design; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202000306
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : Expanding biotransformations : Several metal‐binding noncanonical amino acids have been incorporated into protein scaffolds to create artificial metalloenzymes. We introduced 2‐amino‐3‐(8‐hydroxyquinolin‐3‐yl)propanoic acid (HQAla) into lactococcal multidrug‐resistance regulator (LmrR) and complexed it with several transition metal ions such as Cu II, Zn II and Rh III to showcase its catalytic potential in a variety of different reactions.