A5060590993- Enzyme Catalysis and Immobilization
- Chemical Synthesis and Analysis
- Metal-Catalyzed Oxygenation Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Photosynthetic Processes and Mechanisms
- Carbohydrate Chemistry and Synthesis
- RNA and protein synthesis mechanisms
- Synthetic Organic Chemistry Methods
- Biochemical and Molecular Research
- Biofuel production and bioconversion
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- CRISPR and Genetic Engineering
- biodegradable polymer synthesis and properties
- Virus-based gene therapy research
- Cyclopropane Reaction Mechanisms
- Marine Sponges and Natural Products
- Microbial Natural Products and Biosynthesis
- Porphyrin Metabolism and Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Hemoglobin structure and function
- Enzyme Production and Characterization
- Radical Photochemical Reactions
- Glycosylation and Glycoproteins Research
- Protein purification and stability
University of Manchester
2016-2025
Czech Academy of Sciences, Institute of Biotechnology
2014-2022
Jeremy Benn Associates (United Kingdom)
2022
Prozomix (United Kingdom)
2021
ETH Zurich
2019
Manchester Metropolitan University
2014
University of Nottingham
2012
Institute of Organic Chemistry
2008
Puresyn (United States)
2002-2005
Temple University
1989-1993
The development of cost-effective and sustainable catalytic methods for the production enantiomerically pure chiral amines is a key challenge facing pharmaceutical fine chemical industries. This highlighted by estimate that 40-45% drug candidates contain amine, fueling demand broadly applicable synthetic deliver target structures in high yield enantiomeric excess. Herein we describe application "toolbox" monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable...
The catalytic versatility of pentacoordinated iron is highlighted by the broad range natural and engineered activities heme enzymes such as cytochrome P450s, which position a porphyrin cofactor coordinating central atom below an open substrate binding pocket. This prowess has inspired efforts to design de novo helical bundle scaffolds that bind cofactors. However, designs lack large pocket hence, chemical transformations accessible limited. Here, with goal combining advantages P450 site...
Abstract The widespread application of ω‐transaminases as biocatalysts for chiral amine synthesis has been hampered by fundamental challenges, including unfavorable equilibrium positions and product inhibition. Herein, an efficient process that allows reactions to proceed in high conversion the absence by‐product removal using only one equivalent a diamine donor ( ortho ‐xylylenediamine) is reported. This operationally simple method compatible with most widely used R )‐ S )‐selective ω‐TAs...
Expanding the range of genetically encoded metal coordination environments accessible within tunable protein scaffolds presents excellent opportunities for creation metalloenzymes with augmented properties and novel activities. Here, we demonstrate that installation a noncanonical Nδ-methyl histidine (NMH) as proximal heme ligand in oxygen binding myoglobin (Mb) leads to substantial increases redox potential promiscuous peroxidase activity. Structural characterization this catalytically...
The application of ω-transaminase biocatalysts for the synthesis optically pure chiral amines presents a number challenges, including difficulties associated with displacing challenging reaction equilibria. Herein, we report highly effective approach using low equivalents new diamine donor, cadaverine, which enables high conversions substrates to corresponding in excellent ee. This paves way design self-sufficient fermentation processes combining transaminase biotransformations existing...
Fungal lytic polysaccharide monooxygenases (LPMOs) depolymerise crystalline cellulose and hemicellulose, supporting the utilisation of lignocellulosic biomass as a feedstock for biorefinery biomanufacturing processes. Recent investigations have shown that H2 O2 is most efficient cosubstrate LPMOs. Understanding reaction mechanism LPMOs with therefore importance their use in biotechnological settings. Here, we employed variety spectroscopic biochemical approaches to probe fungal LPMO9C from...
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...
Designing efficient enzymes is a formidable challenge at the forefront of modern biocatalysis. Here, we review recent developments in field and illustrate how interplay between computational design advanced protein engineering has given rise to with diverse activities. Natural proteins have been re-engineered computationally embed designed catalytic sites, affording active catalysts that can be optimized through laboratory evolution enhance efficiency selectivity. Computational tools...
Abstract Directed evolution of computationally designed enzymes has provided new insights into the emergence sophisticated catalytic sites in proteins. In this regard, we have recently shown that a histidine nucleophile and flexible arginine can work synergy to accelerate Morita-Baylis-Hillman (MBH) reaction with unrivalled efficiency. Here, show replacing non-canonical N δ -methylhistidine (MeHis23) leads substantially altered evolutionary outcome which Arg124 been abandoned. Instead, Glu26...
Enzymes rely on complex interactions between precisely positioned active site residues as a mechanism to compensate for the limited functionality contained within genetic code. Heme enzymes provide striking example of this complexity, whereby electronic properties reactive ferryl intermediates are finely tuned through hydrogen bonding proximal ligands and neighboring amino acids. Here, we show that introduction chemically programmed Nδ-methyl histidine (NMH) ligand into an engineered...
The tetrahydro-β-carboline (THBC) ring system is an important structural motif found in a large number of bioactive alkaloid natural products. Herein we report broadly applicable method for the synthesis enantiomerically pure β-carbolines via deracemization procedure employing D9 and D11 variants monoamine oxidase from Aspergillus niger (MAO-N) combination with nonselective chemical reducing agent. Biotransformations were performed on preparative scale, leading to optically enriched products...
The saccharification of wheat straw was improved when an incubation step performed with<italic>Trametes versicolor</italic>laccase (TvL) and the mediator 1-hydroxybenzotriazole (1-HBT) prior to alkaline peroxide extraction (APE).
The lack of robust, high-throughput, and sensitive analytical strategies that can conclusively map the structure glycans has significantly hampered progress in fundamental applied aspects glycoscience. Resolution anomeric α/β glycan linkage within oligosaccharides remains a particular challenge. Here, we show "memory" configuration is retained following gas-phase glycosidic bond fragmentation during tandem mass spectrometry (MS2). These findings allow for integration MS2 with ion mobility...