- Enzyme Production and Characterization
- Biofuel production and bioconversion
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Studies on Chitinases and Chitosanases
- Microbial Metabolites in Food Biotechnology
- Fuel Cells and Related Materials
- Enzyme Structure and Function
- Polysaccharides and Plant Cell Walls
- Streptococcal Infections and Treatments
- Electrocatalysts for Energy Conversion
- Advancements in Solid Oxide Fuel Cells
- Proteoglycans and glycosaminoglycans research
- Microbial Natural Products and Biosynthesis
- Natural product bioactivities and synthesis
- Microbial Metabolic Engineering and Bioproduction
- Mechanical Failure Analysis and Simulation
- Plant nutrient uptake and metabolism
- Enzyme Catalysis and Immobilization
- Antimicrobial Peptides and Activities
- Antimicrobial Resistance in Staphylococcus
- Polyamine Metabolism and Applications
- Extraction and Separation Processes
- Biochemical and Structural Characterization
- Antibiotic Resistance in Bacteria
University of Leeds
2025
University of Lincoln
2016-2024
University of Ulster
2023
University of York
2005-2021
Concordia University
2021
Stanford University
2021
Faraday Technology (United States)
2007-2020
Hester
2016
University of Bath
2006
Simon Fraser University
2006
The capacity of metal-dependent fungal and bacterial polysaccharide oxygenases, termed GH61 CBM33, respectively, to potentiate the enzymatic degradation cellulose opens new possibilities for conversion recalcitrant biomass biofuels. GH61s have already been shown be unique metalloenzymes containing an active site with a mononuclear copper ion coordinated by two histidines, one which is unusual τ-N-methylated N-terminal histidine. We now report structural spectroscopic characterization...
O-GlcNAcase catalyzes the cleavage of beta-O-linked 2-acetamido-2-deoxy-beta-d-glucopyranoside (O-GlcNAc) from serine and threonine residues post-translationally modified proteins. Two potent inhibitors this enzyme are O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) 1,2-dideoxy-2'-methyl-alpha-d-glucopyranoso[2,1-d]-Delta2'-thiazoline (NAG-thiazoline). Derivatives these differ in their selectivity for human over functionally related lysosomal...
Background— Adams–Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In proportion of cases, notable cardiac involvement also apparent. Despite recent advances in the understanding genetic basis AOS, for majority affected subjects, underlying molecular defect remains unresolved. This study aimed to identify novel determinants AOS. Methods Results— Whole-exome sequencing was performed 12 probands, each with clinical diagnosis Analyses...
Endo-β-1,4-xylanases (xylanases), which cleave β-1,4 glycosidic bonds in the xylan backbone, are important components of repertoire enzymes that catalyze plant cell wall degradation. The mechanism by these able to hydrolyze a range decorated xylans remains unclear. Here we reveal three-dimensional structure, determined x-ray crystallography, and catalytic properties Cellvibrio mixtus enzyme Xyn10B (CmXyn10B), most active GH10 xylanase described date. crystal structure complex with...
The endophytic Gram-negative bacterium Gluconacetobacter diazotrophicus SRT4 secretes a constitutively expressed levansucrase (LsdA, EC 2.4.1.10), which converts sucrose into fructooligosaccharides and levan. enzyme is included in GH (glycoside hydrolase) family 68 of the sequence-based classification glycosidases. three-dimensional structure LsdA has been determined by X-ray crystallography at resolution 2.5 Å (1 Å=0.1 nm). was solved molecular replacement using homologous Bacillus subtilis...
The enzymatic degradation of plant cell wall xylan requires the concerted action a diverse syndicate. Among these enzymes are esterases, which hydrolyze O-acetyl substituents, primarily at O-2 position backbone. All acetylxylan esterase structures described previously display alpha/beta hydrolase fold with "Ser-His-Asp" catalytic triad. Here we report two distinct those from Streptomyces lividans and Clostridium thermocellum, in native complex forms, x-ray data to between 1.6 1.0 A...
The cyclic depsipeptide, teixobactin, kills a number of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium tuberculosis without detectable resistance. To date, teixobactin is the only molecule in its class that has shown vivo antibacterial efficacy. In this work, we designed synthesized 10 new ready analogues. These analogues showed highly potent activities against aureus, MRSA, vancomycin-resistant enterococci (VRE) vitro. One analogue,...
The discovery of the new antibiotic teixobactin has been timely in race for unearthing novel antibiotics wherein emergence drug resistant bacteria poses a serious threat worldwide. Herein, we present total syntheses and biological activities two analogues. This approach is simple, efficient several advantages: it uses commercially available building blocks (except AllocHN-d-Thr-OH), single purification step good recovery (22%). By using this have synthesised analogues established that...
The digestion of the plant cell wall requires concerted action a diverse repertoire enzyme activities. An important component these hydrolase consortia are arabinofuranosidases, which release L-arabinofuranose moieties from range structural polysaccharides. anaerobic bacterium Clostridium thermocellum, highly efficient degrader, possesses single α-L-arabinofuranosidase (EC 3.2.1.55), CtAraf51A, located in GH51 (glycoside family 51). crystal structure has been solved native form and...
The enzymatic degradation of the plant cell wall is central both to natural carbon cycle and, increasingly, environmentally friendly routes biomass conversion, including production biofuels. a complex composite cellulose microfibrils embedded in diverse polysaccharides collectively termed hemicelluloses. Xyloglucan one such polysaccharide whose hydrolysis catalyzed by xyloglucanases. Here we present structure Clostridium thermocellum xyloglucanase Xgh74A apo and ligand-complexed forms....
Leu<sub>10</sub>-teixobactin and Ile<sub>10</sub>-teixobactin have shown comparable activity to natural teixobactin.
Enzymes acting on polymeric substrates are frequently classified as exo or endo, reflecting their preference for, ignorance of, polymer chain ends. Most biotechnological applications, especially in the field of polysaccharide degradation, require either endo- exo-acting hydrolases, they harness essential synergy between these two modes action. Here, we have used genomic data tandem with structure to modify, radically, chain-end specificity Cellvibrio japonicus -arabinanase Cj Arb43A. The...
In this work, we have for the first time defined molecular structure of seven teixobactin analogues through variation <sc>d</sc>/<sc>l</sc> configuration its key residues.
ABSTRACT A Late Upper Paleolithic (LUP) site containing Ahrensburgian‐type stone tools has been discovered at South Cuidrach, Isle of Skye, Scotland. Together with a group intertidal circular alignments also recently on the island, this new evidence for occupation northern Scotland represents most northerly LUP in Britain. The timing continental Ahrensburgian culture is closely linked to later part Younger Dryas, known regionally as Loch Lomond Stadial (LLS), cold period that saw significant...
Streptococcus pyogenes (group A Streptococcus) causes severe invasive infections including scarlet fever, pharyngitis (streptococcal sore throat), skin infections, necrotizing fasciitis (flesh-eating disease), septicemia, erysipelas, cellulitis, acute rheumatic and toxic shock. The conversion from nonpathogenic to toxigenic strains of S. is frequently mediated by bacteriophage infection. One the key bacteriophage-encoded virulence factors a putative "hyaluronidase," HylP1, phage tail-fiber...
One of the most intriguing features 90 glycoside hydrolase families (GHs) is range specificities displayed by different members same family, whereas catalytic apparatus and mechanism are often invariant. Family GH26 predominantly comprises beta-1,4 mannanases; however, a bifunctional Clostridium thermocellum member (hereafter CtLic26A) displays markedly specificity. We show that CtLic26A lichenase, specific for mixed (Glcbeta1,4Glcbeta1,4Glcbeta1,3)n oligo- polysaccharides, no activity on...
The enzymatic hydrolysis of alpha-mannosides is catalyzed by glycoside hydrolases (GH), termed alpha-mannosidases. These enzymes are found in different GH sequence-based families. Considerable research has probed the role higher eukaryotic "GH38" that play a key modification and diversification hybrid N-glycans; processes with strong cellular links to cancer autoimmune disease. most extensively studied these Drosophila GH38 alpha-mannosidase II, which been shown be retaining targets both...
We have synthesised <bold>8</bold> simplified, potent teixobactin analogues by replacing <sc>l</sc>-<italic>allo</italic>-enduracididine with its isosteres.
Metal ions such as calcium often play a key role in protein thermostability. The inclusion of metal industrial processes is, however, problematic. Thus, the evolution enzymes that display enhanced stability, which is not reliant on divalent metals, an important biotechnological goal. Here we have used forced to interrogate whether stabilizing effect industrially relevant enzyme can be replaced with amino acid substitutions. Our study has focused GH10 xylanase CjXyn10A from Cellvibrio...
Group A streptococcus (Streptococcus pyogenes) is the causative agent of severe invasive infections such as necrotizing fasciitis (the so-called ‘flesh eating disease’) and toxic-shock syndrome. Spy1600, a glycoside hydrolase from family 84 large superfamily hydrolases, has been proposed to be virulence factor. In present study we show that Spy1600 no activity toward galactosaminides or hyaluronan, but does remove β-O-linked N-acetylglucosamine mammalian glycoproteins – an observation...