Article
Chemistry, Physical
Brandon J. Bloomer, Sean N. Natoli, Marc Garcia-Borras, Jose H. Pereira, Derek B. B. Hu, Paul D. Adams, K. N. Houk, Douglas S. Clark, John F. Hartwig
Summary: Artificial metalloenzymes (ArMs), containing synthetic metal cofactors, are widely used as biocatalysts for unnatural reactions. However, detailed mechanistic information on the effects of protein scaffold on ArM structure and reactivity is limited. This study presents the structure of an unnatural P450 analogue and kinetic analysis of its reaction, revealing a mechanism initiated by cofactor conformational change and highlighting the influence of cofactor dynamics on the catalytic reaction of ArMs.
Article
Chemistry, Multidisciplinary
Sreya Malayam Parambath, Ashley E. Williams, Leigh Anna Hunt, Dhanashree Selvan, Nathan Hammer, Saumen Chakraborty
Summary: This study reports the construction of a de novo-designed artificial hydrogenase (ArH) inspired by [NiFe] hydrogenases, which produces H-2 gas photocatalytically and shows bell-shaped pH-dependence on activity. Spectroscopic studies elucidate the reaction mechanism and a fine balance is found between solution acidity and electron transfer steps for maximizing H-2 production.
Article
Biochemistry & Molecular Biology
Guillermo A. Oliveira Udry, Laura Tiessler-Sala, Eva Pugliese, Agathe Urvoas, Zakaria Halime, Jean-Didier Marechal, Jean-Pierre Mahy, Remy Ricoux
Summary: This study presents the development of a new artificial cobalt hemoprotein by covalently inserting a cobalt heme into the cavity of a protein. This artificial metalloenzyme exhibits catalytic activity for the photo-induced production of H-2 and the reduction of CO2 in a neutral aqueous solution. The coordination of the cobalt ion was completed with the help of an axial glutamine ligand. It was found that burying the cobalt complex in the hydrophobic cavity of the protein significantly enhanced its catalytic activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Kun Yu, Zhi Zou, Nico V. Igareta, Ryo Tachibana, Julia Bechter, Valentin Kohler, Dongping Chen, Thomas R. Ward
Summary: Enantioselective C-H amidation is an attractive method for synthesizing nitrogen-containing molecules with high-added value. This study reports on an artificial metalloenzyme (ArM) consisting of a biotinylated Ir-complex anchored within streptavidin (Sav). The ArM catalyzes the enantioselective amidation of unactivated C(sp (3))-H bonds. Through optimization of the Ir cofactor and Sav, the activity and enantioselectivity were significantly improved, achieving >700 TON and 92% ee for the amidation of unactivated C(sp (3))-H bonds. The crystal structure analysis and QM-MM calculations provide insights into the critical second coordination sphere contacts leading to improved catalytic performance.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Organic
Christopher Adamson, Motomu Kanai
Summary: By integrating non-biological chemical catalysis into the network of life, unique secondary metabolites and value-added materials can be generated. This approach also allows for the production of new diagnostics and therapeutics.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Applied
Yu Chen, Zemin Zhao, Ze Li, Jieying Jing, Wenying Li
Summary: In this study, a series of Ni-Co/NiAlOx catalysts were synthesized by reducing at different temperatures, and the catalytic activity for the hydrogenation of phenanthrene was evaluated. The catalyst reduced at 560 degrees C (Cat-560) showed high activity with a phenanthrene conversion amount of 8.0 mmol·g-1·h-1 and 98% perhydrophenanthrene selectivity. Cat-560 also exhibited superior specific activity and turnover frequency for symmetric octahydrophenanthrene hydrogenation, attributed to its special geometric and electronic structure.
FUEL PROCESSING TECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Vivek Sinha, Elena Khramenkova, Evgeny A. Pidko
Summary: This study investigates the electrocatalytic CO2 reduction reaction (CO2RR) on a silver surface as a representative low-cost model cathode under high cathodic bias, and demonstrates the important role of the electrical double layer (EDL) in catalytic activity and selectivity. By using multiscale modeling, the researchers find that the presence of the EDL hinders the diffusion of CO2 towards the cathode surface, and propose a pathway for CO2 reduction directly over the EDL based on ab initio molecular dynamics simulations. These findings are of significance for the design of more efficient and low-cost CO2RR electrodes.
Article
Chemistry, Physical
Fadri Christoffel, Nico Igareta, Michela M. Pellizzoni, Laura Tiessler-Sala, Boris Lozhkin, Daniel C. Spiess, Agusti Lledos, Jean-Didier Marechal, Ryan L. Peterson, Thomas R. Ward
Summary: Artificial metalloenzymes are created by anchoring an organometallic catalyst within an evolvable protein scaffold, expanding the range of reactions accessible. By designing a specific structure chimeric streptavidin and conducting directed evolution, mutants favoring specific products can be obtained.
Article
Chemistry, Physical
Biswarup Pathak, Amitabha Das, Shyama Charan Mandal, Sandeep Das
Summary: This study models the CuAl2O4(111) surface for CO2 conversion to DME and investigates the importance of dopants in tuning the catalyst's activity. The research highlights the role of Ga in modifying the surface acidity and facilitating methanol conversion to DME, as well as the synergistic effect of Ga and Cu atoms in enhancing the efficiency of CO2 conversion to DME.
JOURNAL OF PHYSICAL CHEMISTRY C
(2022)
Article
Chemistry, Multidisciplinary
Hua-Zhen Duan, Cheng Hu, Yue-Lin Li, Shi-Hao Wang, Yan Xia, Xiaohong Liu, Jiangyun Wang, Yong-Xiang Chen
Summary: This study presents a method to genetically incorporate borane-protected phosphine into proteins, followed by a straightforward one-pot strategy for deboronation and palladium coordination. The genetically encoded phosphine ligand P3BF is expected to greatly expand our ability to design functional metalloproteins.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Li-Jun Zhao, Zequn Yin, Yusheng Shi, Wen Sun, Libo Sun, Huijuan Su, Xun Sun, Weiling Zhang, Linyan Xia, Caixia Qi
Summary: A highly active iridium complex was obtained with an anionic ligand, showing robust cofactor NADH regeneration in physiological conditions. The high activity of the complex can promote enzymatic reactions.
CATALYSIS SCIENCE & TECHNOLOGY
(2021)
Article
Metallurgy & Metallurgical Engineering
Xinran Zhu, Yuexin Han, Yue Cao, Yongsheng Sun, Yanjun Li
Summary: This study characterized the phase transformation and magnetism variation of specularite ore during magnetization roasting using X-ray diffraction, vibrating sample magnetometry, and Mossbauer spectroscopy. It was found that the reduction kinetics of specularite ore followed the nucleation model A(2).
MINERAL PROCESSING AND EXTRACTIVE METALLURGY REVIEW
(2023)
Article
Chemistry, Organic
Alexander R. Nodling, Nicolo Santi, Raquel Castillo, Magdalena Lipka-Lloyd, Yi Jin, Louis C. Morrill, Katarzyna Swiderek, Vicent Moliner, Louis Y. P. Luk
Summary: By combining host screening, protein crystallography, and QM/MM molecular dynamics simulations, the study revealed the impact of protein structure on the catalysis of iminium by biotinylated secondary amines in a model 1,4 conjugate addition reaction. The results showed that the tetrameric host T-Sav was more suitable for the reaction compared to the monomeric streptavidin (M-Sav). Additionally, the Lys121 residues in the asymmetric dimeric variant D-Sav played a critical role in controlling stereoselectivity and reactivity.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Alexandre C. Foucher, Shengsong Yang, Daniel J. Rosen, Jennifer D. Lee, Renjing Huang, Zhiqiao Jiang, Francisco G. Barrera, Kelly Chen, George G. Hollyer, Cynthia M. Friend, Raymond J. Gorte, Christopher B. Murray, Eric A. Stach
Summary: In this study, we report a synthesis method for the preparation of core-shell Cu-Ru, Cu-Rh, and Cu-Ir nanoparticles, with copper as the core and platinum-group metals segregated on the surface. This synthesis method allows for an increase in the surface area of the metals and improves catalytic performance. Additionally, selective etching of the Cu core leads to an increase in active surface area.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Nico V. Igareta, Ryo Tachibana, Daniel C. Spiess, Ryan L. Peterson, Thomas R. Ward
Summary: By anchoring a metal cofactor within a host protein, artificial metalloenzymes can be created that combine the versatility of transition metals with the power of genetic engineering. In this study, a hydrophobic dimerization domain from superoxide dismutase C was engineered onto a streptavidin host-protein to improve second coordination-sphere interactions. The introduction of the dimerization domain resulted in an inversion of configuration and a fivefold increase in catalytic efficiency of the asymmetric transfer hydrogenase.
FARADAY DISCUSSIONS
(2023)
Article
Chemistry, Physical
Holly Jane Davis, Daniel Haeussinger, Thomas R. Ward, Yasunori Okamoto
Article
Multidisciplinary Sciences
Tobias Vornholt, Fadri Christoffel, Michela M. Pellizzoni, Sven Panke, Thomas R. Ward, Markus Jeschek
Summary: Artificial metalloenzymes (ArMs) could play a crucial role in transitioning toward a sustainable economy, but methods for rapidly discovering active ArM variants are needed. A reaction-independent, automation-compatible platform based on biotin-streptavidin technology was introduced to engineer ArMs in Escherichia coli, resulting in up to 15-fold activity enhancements. Smart screening strategies and machine learning models were proposed to accurately predict ArM activity, which has significant implications for future ArM development.
Review
Chemistry, Multidisciplinary
Ariane Stucki, Jaicy Vallapurackal, Thomas R. Ward, Petra S. Dittrich
Summary: Evolution is crucial for the generation of complexity and life, shaping the world over billions of years. While natural evolution is slow and gradual, directed evolution allows for faster optimization of phenotype. The development of versatile tools based on droplet microfluidics has improved the efficiency of enzyme discovery and optimization.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Boris Lozhkin, Thomas R. Ward
Summary: An efficient method for synthesizing monosubstituted aromatic compounds is presented, utilizing ring-closing metathesis followed by spontaneous 1,2-elimination. The method shows high efficiency for late-stage functionalization in various solvents (up to 920 TON) and is compatible with strained cycles and other multiple bonds in the substrate.
HELVETICA CHIMICA ACTA
(2021)
Article
Chemistry, Physical
Sandro Fischer, Thomas R. Ward, Alexandria D. Liang
Summary: Artificial metalloenzymes (ArMs) are created by incorporating synthetic metal catalysts into protein scaffolds, combining the advantages of natural enzymes and synthetic catalysts. The choice of protein scaffold is crucial in tuning the activity of ArMs. The repurposing of the HaloTag protein as an ArM scaffold for metathesis showed promising results in terms of substrate scope and turnover numbers.
Article
Biochemistry & Molecular Biology
Stefano Di Leone, Jaicy Vallapurackal, Saziye Yorulmaz Avsar, Myrto Kyropolou, Thomas R. Ward, Cornelia G. Palivan, Wolfgang Meier
Summary: This study successfully prepared artificial membranes on solid support using the solvent-assisted method, optimized the preparation conditions, evaluated the morphology and mechanical properties, and successfully incorporated biomolecules into the membranes, demonstrating their potential for interacting with biomolecules.
Article
Chemistry, Physical
Alain Baiyoumy, Jaicy Vallapurackal, Fabian Schwizer, Tillmann Heinisch, Tsvetan Kardashliev, Martin Held, Sven Panke, Thomas R. Ward
Summary: Artificial metalloenzymes combine characteristics of both homogeneous catalysts and enzymes, allowing for new-to-nature reactions to be implemented in living organisms. Directed evolution of an artificial metalloenzyme based on Escherichia coli surface-displayed streptavidin led to the assembly of an artificial allylic deallylase, showing catalytic activity towards deprotection reactions. The in vivo screening results showed a significant increase in activity compared to in vitro screening, possibly due to differences in the oligomeric state of the enzyme.
Article
Chemistry, Physical
Fadri Christoffel, Nico Igareta, Michela M. Pellizzoni, Laura Tiessler-Sala, Boris Lozhkin, Daniel C. Spiess, Agusti Lledos, Jean-Didier Marechal, Ryan L. Peterson, Thomas R. Ward
Summary: Artificial metalloenzymes are created by anchoring an organometallic catalyst within an evolvable protein scaffold, expanding the range of reactions accessible. By designing a specific structure chimeric streptavidin and conducting directed evolution, mutants favoring specific products can be obtained.
Article
Chemistry, Multidisciplinary
Alina Stein, Dongping Chen, Nico V. Igareta, Yoann Cotelle, Johannes G. Rebelein, Thomas R. Ward
Summary: Artificial metalloenzymes are hybrid catalysts that anchor a metal cofactor within a host protein to catalyze new-to-nature reactions. In this study, covalent linkage was introduced between the host and guest to improve the localization of a catalyst for enantioselective reduction. Through directed evolution and X-ray analysis, the activity, selectivity, and substrate scope of the catalyst were improved.
ACS CENTRAL SCIENCE
(2021)
Review
Chemistry, Multidisciplinary
Mirjam R. Schreier, Xingwei Guo, Bjorn Pfund, Yasunori Okamoto, Thomas R. Ward, Christoph Kerzig, Oliver S. Wenger
Summary: Cyclometalated iridium(III) complexes are widely used in organic light emitting diodes and photocatalysis for solar energy conversion and synthetic organic chemistry. This article introduces the development of water-soluble variants of these complexes and explores their applications in aqueous photochemistry. The water-soluble complexes have been used in enzyme-catalyzed photoredox reactions, photoionization to yield hydrated electrons, and photochemical upconversion. However, the development of water-soluble photocatalysts still lags behind organic solvents.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Inorganic & Nuclear
Alina Stein, Alexandria Deliz Liang, Reyhan Sahin, Thomas R. Ward
Summary: The potential of artificial metalloenzymes has increased interest in the design of novel metal-binding sites in proteins. Metal-chelating unnatural amino acids provide a promising solution for engineering active metal sites in a defined way. In this study, four metal-chelating unnatural amino acids were introduced into HaloTag, an attractive scaffold for assembling functional artificial metalloenzymes. By complementation with [(eta(5)-C5H5)Ru(MeCN)(3)](+), HaloTag engineered with 2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid (HQ-Ala-1) was used to assemble an artificial metalloenzyme for improved allylic deamination.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2022)
Correction
Chemistry, Physical
Fadri Christoffel, Nico V. Igareta, Michela M. Pellizzoni, Laura Tiessler-Sala, Boris Lozhkin, Daniel C. Spiess, Agusti Lledos, Jean-Didier Marechal, Ryan L. Peterson, Thomas R. Ward
Article
Chemistry, Multidisciplinary
Corentin Rumo, Alina Stein, Juliane Klehr, Ryo Tachibana, Alessandro Prescimone, Daniel Haussinger, Thomas R. Ward
Summary: The selective functionalization of organic compounds is a versatile tool, and artificial metalloenzymes offer an ideal means to modify inert motifs. In this study, quantum mechanics/molecular mechanics simulations were used to identify target residues for genetic optimization of the artificial metalloenzyme. Double-saturation mutagenesis provided detailed insight on the activity and selectivity, leading to the development of artificial metalloenzymes that efficiently catalyze the formation of β- and γ-lactams.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Jaicy Vallapurackal, Ariane Stucki, Alexandria Deliz Liang, Juliane Klehr, Petra S. Dittrich, Thomas R. Ward
Summary: Droplet microfluidics has great potential for ultrahigh-throughput compartmentalization, making it an attractive tool for directed enzyme evolution. In this study, we developed an approach for ultrahigh-throughput screening of an artificial metalloenzyme using commercially available fluorescence-activated cell sorters. The protocol was validated by screening a large library and the results showed good agreement with a traditional screening method. This finding opens up new possibilities for the directed evolution of enzymes using FACS.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Nico V. Igareta, Ryo Tachibana, Daniel C. Spiess, Ryan L. Peterson, Thomas R. Ward
Summary: By anchoring a metal cofactor within a host protein, artificial metalloenzymes can be created that combine the versatility of transition metals with the power of genetic engineering. In this study, a hydrophobic dimerization domain from superoxide dismutase C was engineered onto a streptavidin host-protein to improve second coordination-sphere interactions. The introduction of the dimerization domain resulted in an inversion of configuration and a fivefold increase in catalytic efficiency of the asymmetric transfer hydrogenase.
FARADAY DISCUSSIONS
(2023)
