Breaking Symmetry: Engineering Single-Chain Dimeric Streptavidin as Host for Artificial Metalloenzymes DOI Creative Commons
Shuke Wu, Yi Zhou, Johannes G. Rebelein

и другие.

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(40), С. 15869 - 15878

Опубликована: Сен. 11, 2019

The biotin–streptavidin technology has been extensively exploited to engineer artificial metalloenzymes (ArMs) that catalyze a dozen different reactions. Despite its versatility, the homotetrameric nature of streptavidin (Sav) and noncooperative binding biotinylated cofactors impose two limitations on genetic optimization ArMs: (i) point mutations are reflected in all four subunits Sav, (ii) Sav may lead an erosion catalytic performance, depending cofactor:biotin-binding site ratio. To address these challenges, we report our efforts (monovalent) single-chain dimeric (scdSav) as scaffold for Sav-based ArMs. versatility scdSav host protein is highlighted asymmetric transfer hydrogenation prochiral imines using [Cp*Ir(biot-p-L)Cl] cofactor. By capitalizing more precise fine-tuning biotin-binding vestibule, unrivaled levels activity selectivity were achieved reduction challenging imines. Comparison saturation kinetic data X-ray structures [Cp*Ir(biot-p-L)Cl]·scdSav with structurally related [Cp*Ir(biot-p-L)Cl]·monovalent highlights advantages presence single cofactor precisely localized within vestibule monovalent scdSav. practicality scdSav-based ArMs was illustrated salsolidine precursor (500 mM) afford (R)-salsolidine 90% ee >17 000 TONs. Monovalent thus provides versatile evolve efficient vivo catalysis large-scale applications.

Язык: Английский

The importance of catalytic promiscuity for enzyme design and evolution DOI
Reuben B. Leveson‐Gower, Clemens Mayer, Gérard Roelfes

и другие.

Nature Reviews Chemistry, Год журнала: 2019, Номер 3(12), С. 687 - 705

Опубликована: Ноя. 15, 2019

Язык: Английский

Процитировано

275
Artificial Metalloenzymes: Challenges and Opportunities DOI Creative Commons
Holly J. Davis, Thomas R. Ward

ACS Central Science, Год журнала: 2019, Номер 5(7), С. 1120 - 1136

Опубликована: Июль 16, 2019

Artificial metalloenzymes (ArMs) result from the incorporation of an abiotic metal cofactor within a protein scaffold. From earliest techniques transition metals adsorbed on silk fibers, field ArMs has expanded dramatically over past 60 years to encompass range reaction classes and inspired approaches: Assembly taken multiple forms with both covalent supramolecular anchoring strategies, while scaffolds have been intuitively selected evolved, repurposed, or designed in silico. Herein, we discuss some most prominent recent examples highlight challenges opportunities presented by field.

Язык: Английский

Процитировано

235
Advances in ultrahigh-throughput screening for directed enzyme evolution DOI
Ulrich Markel, Khalil Essani,

Volkan Besirlioglu

и другие.

Chemical Society Reviews, Год журнала: 2019, Номер 49(1), С. 233 - 262

Опубликована: Дек. 9, 2019

This review summarizes how ultrahigh-throughput screening methods employ cells and biomimetic compartments to access the vast, unexplored diversity of biocatalysts with novel functions derived from directed evolution metagenomics libraries.

Язык: Английский

Процитировано

222
A guide to secondary coordination sphere editing DOI
Marcus W. Drover

Chemical Society Reviews, Год журнала: 2022, Номер 51(6), С. 1861 - 1880

Опубликована: Янв. 1, 2022

This tutorial review showcases recent (2015-2021) work describing ligand construction as it relates to the design of secondary coordination spheres (SCSs). Metalloenzymes, for example, utilize SCSs stabilize reactive substrates, shuttle small molecules, and alter redox properties, promoting functional activity. In realm biomimetic chemistry, specific incorporation SCS residues (e.g., Brønsted or Lewis acid/bases, crown ethers, groups etc.) has been shown be equally critical function. contribution illustrates how fundamental advances in organic inorganic chemistry have used such SCSs. These imaginative contributions driven exciting findings many transformations relevant clean fuel generation, including molecule H+, N2, CO2, NOx, O2) reduction. most cases, these reactions occur cooperatively, where both metal are requisite substrate activation.

Язык: Английский

Процитировано

91
Can Machine Learning Revolutionize Directed Evolution of Selective Enzymes? DOI Open Access
Guangyue Li, Yijie Dong, Manfred T. Reetz

и другие.

Advanced Synthesis & Catalysis, Год журнала: 2019, Номер 361(11), С. 2377 - 2386

Опубликована: Март 20, 2019

Abstract Machine learning as a form of artificial intelligence consists algorithms and statistical models for improving computer performance different tasks. Training data are utilized making decisions predictions. Since directed evolution enzymes produces huge amounts potential training data, machine seems to be ideally suited support this protein engineering technique. has been used in science long time with purposes. This mini‐review focuses on the utility an aid selective enzymes. Recent studies have shown that ASRA Innov'SAR well guides when performing saturation mutagenesis at sites lining binding pocket enhancing stereoselectivity activity. magnified image

Язык: Английский

Процитировано

114
Recent Advances in Biocatalysis with Chemical Modification and Expanded Amino Acid Alphabet DOI
Amol D. Pagar, Mahesh D. Patil, Dillon T. Flood

и другие.

Chemical Reviews, Год журнала: 2021, Номер 121(10), С. 6173 - 6245

Опубликована: Апрель 22, 2021

The two main strategies for enzyme engineering, directed evolution and rational design, have found widespread applications in improving the intrinsic activities of proteins. Although numerous advances been achieved using these ground-breaking methods, limited chemical diversity biopolymers, restricted to 20 canonical amino acids, hampers creation novel enzymes that Nature has never made thus far. To address this, much research devoted expanding protein sequence space via modifications and/or incorporation noncanonical acids (ncAAs). This review provides a balanced discussion critical evaluation applications, recent advances, technical breakthroughs biocatalysis three approaches: (i) modification cAAs, (ii) ncAAs, (iii) incorporated ncAAs. Furthermore, approaches result on functional properties mechanistic study are extensively reviewed. We also discuss design artificial with ncAAs incorporated. Finally, we current challenges future perspectives expanded acid alphabet.

Язык: Английский

Процитировано

94
Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies DOI
Guangfan Zheng, Zhi Zhou, Guoxun Zhu

и другие.

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(7), С. 2890 - 2896

Опубликована: Дек. 9, 2019

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio- and diastereoselective construction of cyclopropanes through C-H activation arenes coupling with readily available cyclopropenes is highly appealing but remains challenge. A dual directing-group-assisted strategy was used to realize mild redox-neutral RhIII -catalyzed cyclopropylation N-phenoxylsulfonamides enantioselective, diastereoselective, regioselective fashion cyclopropenyl secondary alcohols as cyclopropylating reagent. Synthetic applications demonstrated highlight the potential developed method. Integrated experimental computational mechanistic studies revealed that reaction proceeds via RhV nitrenoid intermediate, Noyori-type outer sphere concerted proton-hydride transfer from alcohol Rh=N bond produces observed trans selectivity.

Язык: Английский

Процитировано

88
De novo metalloprotein design DOI
Matthew J. Chalkley, Samuel I. Mann, William F. DeGrado

и другие.

Nature Reviews Chemistry, Год журнала: 2021, Номер 6(1), С. 31 - 50

Опубликована: Дек. 6, 2021

Язык: Английский

Процитировано

86
Engineering and emerging applications of artificial metalloenzymes with whole cells DOI

Malte Wittwer,

Ulrich Markel, Johannes Schiffels

и другие.

Nature Catalysis, Год журнала: 2021, Номер 4(10), С. 814 - 827

Опубликована: Окт. 20, 2021

Язык: Английский

Процитировано

60
Revealing the Nature of the Second Branch Point in the Catalytic Mechanism of the Fe(II)/2OG-Dependent Ethylene Forming Enzyme DOI Creative Commons
Simahudeen Bathir Jaber Sathik Rifayee, Midhun George Thomas, Christo Christov

и другие.

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The study explores the second branchpoint of EFE catalytic mechanism, which determines product distribution ethylene and 3-hydroxypropionate formation using QM/MM simulations on WT A198L variants EFE.

Язык: Английский

Процитировано

1