Boron Designer Enzyme with a Hybrid Catalytic Dyad DOI Creative Commons
Lars Longwitz,

Marijn D. Kamer,

Bart Brouwer

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(24), P. 18469 - 18476

Published: Dec. 3, 2024

Genetically encoded noncanonical amino acids can introduce new-to-nature activation modes into enzymes. While these act as catalysts on their own due to inherent chemical properties, interactions with adjacent residues in an enzyme, such those present natural catalytic dyads or triads, unlock a higher potential for designer We incorporated boron-containing acid the protein scaffold RamR create active enzyme kinetic resolution of α-hydroxythioesters. found that closely positioned lysine residue is crucial activity by forming hybrid dyad boronic residue. The capable resolving differently substituted α-hydroxythioesters good selectivities. High-resolution mass spectrometry, 11B NMR spectroscopy, and crystal structure analysis gave insight three steps mechanism (substrate binding, hydroxide transfer, product release). Mutations around led variant 2-fold improvement selectivity.

Language: Английский

Noncanonical Amino Acids: Bringing New-to-Nature Functionalities to Biocatalysis DOI Creative Commons
Bart Brouwer, Franco Della‐Felice, Jan Hendrik Illies

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(19), P. 10877 - 10923

Published: Sept. 27, 2024

Biocatalysis has become an important component of modern organic chemistry, presenting efficient and environmentally friendly approach to synthetic transformations. Advances in molecular biology, computational modeling, protein engineering have unlocked the full potential enzymes various industrial applications. However, inherent limitations natural building blocks sparked a revolutionary shift.

Language: Английский

Citations

4
Creation and optimization of artificial metalloenzymes: Harnessing the power of directed evolution and beyond DOI Creative Commons
Zhi Zou,

Bradley Higginson,

Thomas R. Ward

et al.

Chem, Journal Year: 2024, Volume and Issue: 10(8), P. 2373 - 2389

Published: Aug. 1, 2024

Rising demands for efficient, selective, and versatile synthetic methods call new enzymatic functions that may not be available in the biological realm. The challenges are daunting, requiring enzymes to take on newly developed biocatalysts exhibit activity selectivity comparable or better than current chemocatalytic fill gaps chemistry. In this perspective, we summarize status of non-natural biocatalysis describe how protein engineering, particularly directed evolution integrated with chemical rationalization, enables innovations expand space accessible enzymes. creation abiological represents a growing area research requires knowledge from different fields, including enzymology,

Language: Английский

Citations

1
Exchange of Equatorial Ligands in Protein-bound Paddlewheel Ru25+ Complexes: New Insights form X-ray Crystallography and Quantum Chemistry DOI Creative Commons
Aarón Terán, Francesca Fasulo, Giarita Ferraro

et al.

Inorganic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

The reactivity of [Ru 2 Cl(D- p -CNPhF)(O CCH 3 ) ] n (D- -CNPhF − = N , ′-bis(4-cyanophenyl)formamidinate) with the model protein RNase A has been investigated by X-ray crystallography and Quantum Chemistry.

Language: Английский

Citations

0
Rational Design of an Artificial Metalloenzyme by Constructing a Metal-Binding Site Close to the Heme Cofactor in Myoglobin DOI

Lv-Suo Nie,

Xichun Liu,

Lu Yu

et al.

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching nonnative ligand of bipyridine Cys46 through F46C mutation distal site. The X-ray structure designed enzyme, termed F46C-mBpy Mb, was solved Cu(II)-bound form, which revealed formation heterodinuclear center Cu-His-H

Language: Английский

Citations

0
Hybrid Metal Catalysts as Valuable Tools in Organic Synthesis: An Overview of the Recent Advances in Asymmetric C─C Bond Formation Reactions DOI Creative Commons
Isabella Rimoldi, Giulia Coffetti, Raffaella Gandolfi

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(21), P. 5090 - 5090

Published: Oct. 28, 2024

Carbon–carbon bond formation represents a key reaction in organic synthesis, resulting paramount importance for constructing the carbon backbone of molecules. However, traditional metal-based catalysis, despite its advantages, often struggles with issues related to efficiency, selectivity, and sustainability. On other hand, while biocatalysis offers superior selectivity due an extraordinary recognition process substrate, scope applicable reactions remains somewhat limited. In this context, Artificial Metalloenzymes (ArMs) Metallo Peptides (MPs) offer promising not fully explored solution, merging two fields transition metal catalysis biotransformations, by inserting catalytically active cofactor into customizable protein scaffold or coordinating ion directly short tunable amino acid (Aa) sequence, respectively. As result, these hybrid catalysts have gained attention as valuable tools challenging catalytic transformations, providing systems new-to-nature properties synthesis. This review overview recent advances development ArMs MPs, focusing on their application asymmetric carbon–carbon bond-forming reactions, such carbene insertion, Michael additions, Friedel–Crafts cross-coupling cyclopropanation, underscoring versatility synthesizing biologically relevant compounds.

Language: Английский

Citations

0
Expanding the scope of copper artificial metalloenzymes: A potential fluorinase? DOI Creative Commons

Isabeau Lüddecke,

Amanda G. Jarvis

Journal of Inorganic Biochemistry, Journal Year: 2024, Volume and Issue: 263, P. 112777 - 112777

Published: Nov. 19, 2024

Language: Английский

Citations

0
Boron Designer Enzyme with a Hybrid Catalytic Dyad DOI Creative Commons
Lars Longwitz,

Marijn D. Kamer,

Bart Brouwer

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(24), P. 18469 - 18476

Published: Dec. 3, 2024

Genetically encoded noncanonical amino acids can introduce new-to-nature activation modes into enzymes. While these act as catalysts on their own due to inherent chemical properties, interactions with adjacent residues in an enzyme, such those present natural catalytic dyads or triads, unlock a higher potential for designer We incorporated boron-containing acid the protein scaffold RamR create active enzyme kinetic resolution of α-hydroxythioesters. found that closely positioned lysine residue is crucial activity by forming hybrid dyad boronic residue. The capable resolving differently substituted α-hydroxythioesters good selectivities. High-resolution mass spectrometry, 11B NMR spectroscopy, and crystal structure analysis gave insight three steps mechanism (substrate binding, hydroxide transfer, product release). Mutations around led variant 2-fold improvement selectivity.

Language: Английский

Citations

0