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

• Published in: Chembiochem : a European journal of chemical biology Vol. 21; no. 21; pp. 3077 - 3081
• Main Authors: Drienovská, Ivana, Scheele, Remkes A., Gutiérrez de Souza, Cora, Roelfes, Gerard
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 02-11-2020; John Wiley and Sons Inc
• Subjects: Alanine; Alkylation; Amino acids; biocatalysis; Communication; Communications; Enzymes; hybrid catalysts; Hydrolase; Hydroxyquinoline; Metal ions; metalloenzymes; noncanonical amino acids; protein design; Stop codon; Transition metals; hybrid catalysts; noncanonical amino acids; protein design; biocatalysis; metalloenzymes
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202000306

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.
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 CuII, ZnII and RhIII to showcase its catalytic potential in a variety of different reactions.