Artificial Gold Enzymes Using a Genetically Encoded Thiophenol‐Based Noble‐Metal‐Binding Ligand

to related objects

Abstract: Incorporating noble metals in artificial metalloenzymes (ArMs) is challenging due to the lack of suitable soft coordinating ligands among natural amino acids. We present a new class of ArMs featuring a genetically encoded noble‐metal‐binding site based on a non‐canonical thiophenol‐based amino acid, 4‐mercaptophenylalanine (pSHF), incorporated in the transcriptional regulator LmrR through stop codon suppression. We demonstrate that pSHF is an excellent ligand for noble metals in their low oxidation states. The corresponding gold (I) enzyme was characterised by mass spectrometry, UV/Vis spectroscopy and X‐ray crystallography and successfully catalysed hydroamination reactions of 2‐ethynyl anilines with turnover numbers over 50. Interestingly, two equivalents of gold (I) per protein dimer proved to be required for activity. Up to 98 % regioselectivity in the hydroamination of an ethynylphenylurea substrate was observed, yielding the corresponding phenyl‐dihydroquinazolinone product, consistent with a π‐activation mechanism by single gold centres. The ArM was optimized by site saturation mutagenesis using an on‐bead screening protocol. This resulted in a single mutant that showed higher activity for one class of substrates. This work brings the power of noble‐metal catalysis into the realm of enzyme engineering and establishes thiophenols as alternative ligands for noble metals, providing new opportunities in coordination chemistry and catalysis.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Artificial Gold Enzymes Using a Genetically Encoded Thiophenol‐Based Noble‐Metal‐Binding Ligand ; day:17 ; month:12 ; year:2024 ; extent:10
Angewandte Chemie / International edition. International edition ; (17.12.2024) (gesamt 10)

Creator: Veen, Mathijs J.
Aalbers, Friso S.
Rozeboom, Henriëtte J.
Thunnissen, Andy‐Mark W. H.
Sauer, Daniel F.
Roelfes, Gerard

DOI: 10.1002/anie.202421912

URN: urn:nbn:de:101:1-2412171326310.824656946774

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:28 AM CEST

Data provider

This object is provided by:
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.

Show original at data provider

Associated

Veen, Mathijs J.
Aalbers, Friso S.
Rozeboom, Henriëtte J.
Thunnissen, Andy‐Mark W. H.
Sauer, Daniel F.
Roelfes, Gerard

Other Objects (12)