Thomas R. Ward
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View article: Programmable Artificial-Cellular Membrane Dynamics via Ring-Closing Metathesis
Programmable Artificial-Cellular Membrane Dynamics via Ring-Closing Metathesis Open
Lateral phase-separated structures in cellular membranes serve as functional domains in various membrane-mediated biological processes. Controlling phase-separation dynamics through catalysis could enable the assembly of smart vesicles tha…
View article: Of Revolutions and Roadblocks: The Emerging Role of Machine Learning in Biocatalysis
Of Revolutions and Roadblocks: The Emerging Role of Machine Learning in Biocatalysis Open
Machine learning (ML) is rapidly turning into a key technology for biocatalysis. By learning patterns in amino acid sequences, protein structures, and functional data, ML models can help navigate complex fitness landscapes, uncover new enz…
View article: What Can be Learned From the Electrostatic Environments Within Nitrogenase Enzymes?
What Can be Learned From the Electrostatic Environments Within Nitrogenase Enzymes? Open
Nitrogen fixation is a fundamental, and yet challenging, chemical transformation due to the intrinsic inertness of dinitrogen. Whereas industrial ammonia synthesis relies on the energy‐intensive Haber–Bosch process, nitrogenase enzymes ach…
View article: What can be learned from the electrostatic environments within nitrogenase enzymes?
What can be learned from the electrostatic environments within nitrogenase enzymes? Open
Nitrogen fixation is a fundamental, and yet challenging, chemical transformation due to the intrinsic inertness of dinitrogen. Whereas industrial ammonia synthesis relies on the energy-intensive Haber–Bosch process, nitrogenase enzymes ach…
View article: Canadian consensus for the assessment and testing of Lynch syndrome
Canadian consensus for the assessment and testing of Lynch syndrome Open
Background Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome caused by a germline pathogenic variant, or epigenetic silencing, of a mismatch repair (MMR) gene, leading to a wide cancer spectrum with gene-specific …
View article: Permeabilisation of the Outer Membrane of <scp> <i>Escherichia coli</i> </scp> for Enhanced Transport of Complex Molecules
Permeabilisation of the Outer Membrane of <span> <i>Escherichia coli</i> </span> for Enhanced Transport of Complex Molecules Open
The bacterial envelope plays a critical role in maintaining essential cellular functions by selectively regulating import and export. The selectivity of this envelope can restrict the utilisation of externally provided compounds, thereby r…
View article: An application of nowcasting methods: Cases of norovirus during the winter 2023/2024 in England
An application of nowcasting methods: Cases of norovirus during the winter 2023/2024 in England Open
Background Norovirus is a leading cause of acute gastroenteritis, adding to strain on healthcare systems. Diagnostic test reporting of norovirus is often delayed, resulting in incomplete data for real-time surveillance. Methods To nowcast …
View article: What can be learned from the electrostatic environments within nitrogenase enzymes?
What can be learned from the electrostatic environments within nitrogenase enzymes? Open
Nitrogen fixation is a fundamental, and yet challenging, chemical transformation due to the intrinsic inertness of dinitrogen (N₂). Whereas industrial ammonia synthesis relies on the energy-intensive Haber–Bosch process, nitrogenase enzyme…
View article: De Novo Design and Evolution of an Artificial Metathase for Cytoplasmic Olefin Metathesis
De Novo Design and Evolution of an Artificial Metathase for Cytoplasmic Olefin Metathesis Open
Artificial metalloenzymes (ArMs) present a promising avenue for abiotic catalysis within living systems. However, their in vivo application is currently limited by critical challenges, particularly in selecting suitable protein scaffolds c…
View article: What can be learned from the electrostatic environments within nitrogenase enzymes?
What can be learned from the electrostatic environments within nitrogenase enzymes? Open
Nitrogen fixation is a fundamental, and yet challenging, chemical transformation due to the intrinsic inertness of dinitrogen (N₂). Whereas industrial ammonia synthesis relies on the energy-intensive Haber–Bosch process, nitrogenase enzyme…
View article: Artificial Metalloenzymes with Two Catalytic Cofactors for Tandem Abiotic Transformations
Artificial Metalloenzymes with Two Catalytic Cofactors for Tandem Abiotic Transformations Open
Artificial metalloenzymes (ArMs) enable the integration of abiotic cofactors within a native protein scaffold, allowing for non‐natural catalytic activities. Previous ArMs, however, have primarily relied on single cofactor systems, limitin…
View article: Artificial Metalloenzymes with Two Catalytic Cofactors for Tandem Abiotic Transformations
Artificial Metalloenzymes with Two Catalytic Cofactors for Tandem Abiotic Transformations Open
Artificial metalloenzymes (ArMs) enable the integration of abiotic cofactors within a native protein scaffold, allowing for non‐natural catalytic activities. Previous ArMs, however, have primarily relied on single cofactor systems, limitin…
View article: Repurposing hemoproteins for metal-catalyzed H atom transfer in asymmetric radical biocatalysis
Repurposing hemoproteins for metal-catalyzed H atom transfer in asymmetric radical biocatalysis Open
Transition metal–hydrides have been widely exploited in homogenous catalysis for hydrofunctionalization of unsaturated moieties, including carbonyls, alkenes and alkynes. As a complement to the well-established chemistry of these complexes…
View article: The Impact of Healthcare Pressures on the COVID-19 Hospitalisation Fatality Risk in England
The Impact of Healthcare Pressures on the COVID-19 Hospitalisation Fatality Risk in England Open
Background As the impact of the SARS-CoV-2 pandemic extends into 2023 and beyond, the treatment and outcomes of infected patients continues to evolve. Unlike earlier in the pandemic there are now further infectious disease pressures placed…
View article: Biotin-Independent<i>Saccharomyces cerevisiae</i>with Enhanced Growth: Engineering an Acetyl-CoA Carboxylase Bypass
Biotin-Independent<i>Saccharomyces cerevisiae</i>with Enhanced Growth: Engineering an Acetyl-CoA Carboxylase Bypass Open
Throughout evolution, most Saccharomyces cerevisiae strains have lost their ability to synthesize biotin, an essential cofactor of several carboxylating enzymes. As a result, the essential vitamin or its precursors must be uptaken from the…
View article: Creation and optimization of artificial metalloenzymes: Harnessing the power of directed evolution and beyond
Creation and optimization of artificial metalloenzymes: Harnessing the power of directed evolution and beyond Open
Rising demands for efficient, selective, and versatile synthetic methods call for new enzymatic functions that may not be available in the biological realm. The challenges are daunting, requiring enzymes to take on new functions and requir…
View article: An Evolved Artificial Radical Cyclase Enables the Construction of Bicyclic Terpenoid Scaffolds via an H-Atom Transfer Pathway
An Evolved Artificial Radical Cyclase Enables the Construction of Bicyclic Terpenoid Scaffolds via an H-Atom Transfer Pathway Open
While natural terpenoid cyclases generate complex terpenoid structures via cationic mechanisms, alternative radical cyclization pathways are underexplored. The metal-catalyzed hydrogen-atom-transfer (M-HAT) reaction offers an attractive me…
View article: Repurposing myoglobin into an abiological asymmetric ketoreductase
Repurposing myoglobin into an abiological asymmetric ketoreductase Open
Thanks to recent advances in enzyme repurposing, hemoproteins have gained significant attention as versatile biocatalysts that catalyze a variety of transformations, ranging from oxidation to redox-neutral reactions. To complement these ac…
View article: Pnictogen‐Bonding Enzymes
Pnictogen‐Bonding Enzymes Open
The objective of this study was to create artificial enzymes that capitalize on pnictogen bonding, a σ‐hole interaction that is essentially absent in biocatalysis. For this purpose, stibine catalysts were equipped with a biotin derivative …
View article: Pnictogen‐Bonding Enzymes
Pnictogen‐Bonding Enzymes Open
The objective of this study was to create artificial enzymes that capitalize on pnictogen bonding, a σ‐hole interaction that is essentially absent in biocatalysis. For this purpose, stibine catalysts were equipped with a biotin derivative …
View article: Enhanced Sequence-Activity Mapping and Evolution of Artificial Metalloenzymes by Active Learning
Enhanced Sequence-Activity Mapping and Evolution of Artificial Metalloenzymes by Active Learning Open
Tailored enzymes are crucial for the transition to a sustainable bioeconomy. However, enzyme engineering is laborious and failure-prone due to its reliance on serendipity. The efficiency and success rates of engineering campaigns may be im…
View article: Artificial Metalloenzyme‐Catalyzed Enantioselective Carboamination of Alkenes
Artificial Metalloenzyme‐Catalyzed Enantioselective Carboamination of Alkenes Open
Relying on ubiquitous alkenes, carboamination reactions enable the difunctionalization of the double bond by the concurrent formation of a C−N and a C−C single bond. In the past years, several groups have reported on elegant strategies for…
View article: The Two Janus Faces of CpRu‐Based Deallylation Catalysts and Their Application for <i>in Cellulo</i> Prodrug Uncaging
The Two Janus Faces of CpRu‐Based Deallylation Catalysts and Their Application for <i>in Cellulo</i> Prodrug Uncaging Open
In the past 18 years, metal‐catalyzed deallylation has proven a useful tool for studying biological processes in cellulo and in the early development of innovative therapeutic catalytic strategies. This reaction is catalyzed by Ru‐piano st…
View article: Artificial Metalloenzyme Catalyzed Enantioselective Carboamination of Alkenes
Artificial Metalloenzyme Catalyzed Enantioselective Carboamination of Alkenes Open
Relying on ubiquitous alkenes, carboamination reactions enable the difunctionalization of the double bond by the concurrent formation of a C–N and a C–C single bond. In the past years, several groups have reported on elegant strategies for…
View article: Enhanced Sequence-Activity Mapping and Evolution of Artificial Metalloenzymes by Active Learning
Enhanced Sequence-Activity Mapping and Evolution of Artificial Metalloenzymes by Active Learning Open
Tailored enzymes hold great potential to accelerate the transition to a sustainable bioeconomy. Yet, enzyme engineering remains challenging as it relies largely on serendipity and is, therefore, highly laborious and prone to failure. The e…
View article: The two Janus faces of CpRu-based deallylation catalysts and their application for in cellulo prodrug uncaging.
The two Janus faces of CpRu-based deallylation catalysts and their application for in cellulo prodrug uncaging. Open
In the past 16 years, metal-catalyzed deallylation has proven a useful tool for studying biological processes in cellulo and in the early development of innovative therapeutic catalytic strategies. This reaction is catalyzed by Ru-piano st…