A5085318182- Enzyme Catalysis and Immobilization
- Biochemical and Molecular Research
- Chemical Synthesis and Analysis
- Pancreatic function and diabetes
- Tuberculosis Research and Epidemiology
- Asymmetric Hydrogenation and Catalysis
- Epigenetics and DNA Methylation
- Microbial Metabolic Engineering and Bioproduction
- RNA and protein synthesis mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- RNA modifications and cancer
- Catalysis for Biomass Conversion
- HIV/AIDS drug development and treatment
- X-ray Diffraction in Crystallography
- Amino Acid Enzymes and Metabolism
- Enzyme Structure and Function
- Crystallization and Solubility Studies
- Computational Drug Discovery Methods
- Cyclopropane Reaction Mechanisms
- Carbohydrate Chemistry and Synthesis
- Biochemical Acid Research Studies
- Click Chemistry and Applications
- Enzyme Production and Characterization
- Synthesis and Catalytic Reactions
- Innovative Microfluidic and Catalytic Techniques Innovation
University of Manchester
2019-2025
Scripps Institution of Oceanography
2024
University of California, San Diego
2024
Prozomix (United Kingdom)
2021
The Covid-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process Molnupiravir, nucleoside analogue recently approved as an orally available treatment SARS-CoV-2. Key success of this was development efficient biocatalyst production N-hydroxy-cytidine through evolutionary adaption hydrolytic enzyme cytidine deaminase. This engineered performs >85 000 turnovers in less than 3 h, operates...
In the wake of Covid-19 pandemic, it has become clear that global access to efficacious antiviral drugs will be critical combat future outbreaks SARS-CoV-2 or related viruses. The orally available main protease inhibitor nirmatrelvir proven an effective treatment option for Covid-19, especially in compromised patients. We report a new synthesis featuring highly enantioselective biocatalytic desymmetrization (>99% ee) and diastereoselective multicomponent reaction (>25:1 dr) as key steps. Our...
Abstract Reductive aminases (RedAms) have recently emerged as promising biocatalysts for the synthesis of chiral secondary amines by coupling primary with aldehydes/ketones. However, access to tertiary remains more problematic, particularly when ketones amines. Here we show that scope these enzymes can be extended allow selective reductive aminations cyclic amines, such piperidines and morpholines, both aldehydes ketones. These biotransformations provide important motifs found in active...
The availability of an expanded genetic code opens exciting new opportunities in enzyme design and engineering. In this regard histidine analogues have proven particularly versatile, serving as ligands to augment metalloenzyme function catalytic nucleophiles designed enzymes. ability genetically encode multiple functional residues could greatly expand the range chemistry accessible within active sites. Here, we develop mutually orthogonal translation components selectively two structurally...
Herein we report the conversion of cytidine 2 to N-hydroxycytidine 7 catalysed by deaminase (CD). The wild-type enzyme operates efficiently at high sustrate loadings and hydroxylamine concentrations favor N-hydroxy-cytidine formation over uridine. Although demonstrated good activity, were able further enhance ratio uridine produced through directed evolution CD. In particular, a T123G mutation close active site dramatically reduces hydrolysis activity whilst preserving desired amination...
We report a new synthesis of the Covid-19 drug nirmatrelvir featuring highly enantioselective biocatalytic desymmetrization and diastereoselective multicomponent reaction as key steps. Our route avoids use transition metals peptide coupling reagents, resulting in an overall atom-economic process.
The COVID-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process Molnupiravir, nucleoside analogue currently in phase 3 clinical trials as an orally available treatment SARS-CoV-2. Key success of this was development cytidine aminotransferase production N-hydroxy-cytidine through evolutionary adaption hydrolytic enzyme deaminase. This engineered biocatalyst performs >100,000...
Herein we report the conversion of cytidine 2 to N-hydroxycytidine 7 catalysed by deaminase (CD). The wild-type enzyme operates efficiently at high sustrate loadings and hydroxylamine concentrations favor N-hydroxy-cytidine formation over uridine. Although demonstrated good activity, were able further enhance ratio uridine produced through directed evolution CD. In particular, a T123G mutation close active site dramatically reduces hydrolysis activity whilst preserving desired amination...
The COVID-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process Molnupiravir, nucleoside analogue currently in phase 3 clinical trials as an orally available treatment SARS-CoV-2. Key success of this was development cytidine aminotransferase production N-hydroxy-cytidine through evolutionary adaption hydrolytic enzyme deaminase. This engineered biocatalyst performs >100,000...
The COVID-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process Molnupiravir, nucleoside analogue currently in phase 3 clinical trials as an orally available treatment SARS-CoV-2. Key success of this was development cytidine aminotransferase production N-hydroxy-cytidine through evolutionary adaption hydrolytic enzyme deaminase. This engineered biocatalyst performs >100,000...
The COVID-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process Molnupiravir, nucleoside analogue currently in phase 3 clinical trials as an orally available treatment SARS-CoV-2. Key success of this was development cytidine aminotransferase production N-hydroxy-cytidine through evolutionary adaption hydrolytic enzyme deaminase. This engineered biocatalyst performs >100,000...