A5070568728- Enzyme Production and Characterization
- Biofuel production and bioconversion
- Glycosylation and Glycoproteins Research
- Polysaccharides and Plant Cell Walls
- Carbohydrate Chemistry and Synthesis
- Microbial Metabolites in Food Biotechnology
- Gut microbiota and health
- Probiotics and Fermented Foods
- Enzyme Structure and Function
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Catalysis and Immobilization
- Genomics and Phylogenetic Studies
- Microbial Natural Products and Biosynthesis
- Bacterial Genetics and Biotechnology
- Legume Nitrogen Fixing Symbiosis
- Advanced Cellulose Research Studies
- Plant nutrient uptake and metabolism
- Plant-Microbe Interactions and Immunity
- Digestive system and related health
- Food composition and properties
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Transgenic Plants and Applications
- Seaweed-derived Bioactive Compounds
- Microbial Community Ecology and Physiology
Newcastle University
2015-2025
University of Birmingham
2022
Collaborative Group (United States)
2021
Christ University
2010
University of East Anglia
2005
University of Oxford
2005
University of Sheffield
2001-2003
University of York
2000-2002
Lund University
2002
University of Glasgow
2001
Symbiotic bacteria inhabiting the human gut have evolved under intense pressure to utilize complex carbohydrates, primarily plant cell wall glycans in our diets. These polysaccharides are not digested by enzymes, but processed absorbable short chain fatty acids bacteria. The Bacteroidetes, one of two dominant bacterial phyla adult gut, possess broad glycan-degrading abilities. species use a series membrane protein complexes, termed Sus-like systems, for catabolism many carbohydrates....
Abstract The structure of the human gut microbiota is controlled primarily through degradation complex dietary carbohydrates, but extent to which carbohydrate breakdown products are shared between members unclear. We show here, using xylan as a model, that sharing carbohydrates by key microbiota, such Bacteroides ovatus , dependent on complexity target glycan. Characterization extensive degrading apparatus expressed B. reveals polysaccharide significantly more than previous models suggested,...
The interaction between xylan and cellulose microfibrils is important for secondary cell wall properties in vascular plants; however, the molecular arrangement of nature bonding polysaccharides are unknown. In dicots, backbone β-(1,4)-linked xylosyl residues decorated by occasional glucuronic acid, approximately one-half O-acetylated at C-2 or C-3. We recently proposed that even, periodic spacing GlcA major domain dicot might allow to fold as a twofold helical screw facilitate alignment...
Humans, like all mammals, depend on the gut microbiome for digestion of cellulose, main component plant fiber. However, evidence cellulose fermentation in human is scarce. We have identified ruminococcal species microbiota populations that assemble functional multienzymatic cellulosome structures capable degrading cell wall polysaccharides. One these species, which strongly associated with humans, likely originated ruminant and was subsequently transferred to gut, potentially during...
Akkermansia muciniphila is a human microbial symbiont residing in the mucosal layer of large intestine. Its main carbon source highly heterogeneous mucin glycoprotein, and it uses an array carbohydrate-active enzymes sulfatases to access this complex energy source. Here we describe biochemical characterization 54 glycoside hydrolases, 11 1 polysaccharide lyase from A. provide holistic understanding their carbohydrate-degrading activities. This was achieved using variety liquid chromatography...
To investigate the mode of action cellulose-binding domains (CBDs), Type II CBD from Pseudomonas fluorescenssubsp. cellulosaxylanase A (XYLACBD) and cellulase E (CELECBD) were expressed as individual entities or fused to catalytic domain a Clostridium thermocellumendoglucanase (EGE). The two CBDs exhibited similar Ka values for bacterial microcrystalline cellulose (CELECBD, 1.62×106 M-1; XYLACBD, 1.83×106 M-1) acid-swollen 1.66×106 1.73×106 M-1). NMR spectra XYLACBD titrated with...
Plant cell walls are degraded by glycoside hydrolases that often contain noncatalytic carbohydrate-binding modules (CBMs), which potentiate degradation. There currently 11 sequence-based cellulose-directed CBM families; however, the biological significance of structural diversity displayed these protein is uncertain. Here we interrogate capacity eight cellulose-binding CBMs to bind walls. These target crystalline cellulose (type A) and located in families 1, 2a, 3a, 10 (CBM1, CBM2a, CBM3a,...
Significance The major nutrients available to the human microbiota are complex carbohydrates. Host glycans important this microbial community, particularly when dietary carbohydrates scarce. host heparin and heparan sulfate high-priority for Bacteroides thetaiotaomicron , a member of microbiota. degradation these is challenging, reflecting their highly variable sulfation patterns. How bacteria have adapted depolymerize myriad substructures class glycosaminoglycan unknown. Here, we show how...
The mucosal microbiota is recognised as an important factor for our health, with many disease states linked to imbalances in the normal community structure. Hence, there considerable interest identifying molecular basis of human-microbe interactions. In this work we investigated capacity microbes thrive on surfaces, either mutualists, commensals or pathogens, using comparative genomics identify co-occurring traits. We identified a novel domain named M60-like/PF13402 (new Pfam entry PF13402),...
Abstract The thick mucus layer of the gut provides a barrier to infiltration underlying epithelia by both normal microbiota and enteric pathogens. Some members utilise mucin glycoproteins as nutrient source, but detailed understanding mechanisms used breakdown these complex macromolecules is lacking. Here we describe discovery characterisation endo-acting enzymes from prominent mucin-degrading bacteria that target polyLacNAc structures within oligosaccharide side chains animal human mucins....
Abstract In Bacteroidetes, one of the dominant phyla mammalian gut, active uptake large nutrients across outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features function in glycan remain unclear, including ligand binding, role SusD lid and size limit for substrate transport. Here we characterise β2,6 fructo-oligosaccharide (FOS) importing from Bacteroides thetaiotaomicron (Bt1762-Bt1763) to shed light on function. Co-crystal...
Many polysaccharide-degrading enzymes display a modular structure in which catalytic module is attached to one or more noncatalytic modules. Several xylanases contain of previously unknown function (termed "X6" modules) that had been implicated thermostability. We have investigated the properties two such "thermostabilizing" modules, X6a and X6b from Clostridium thermocellum xylanase Xyn10B. These expressed either as discrete entities their natural fusions with module, were assayed, capacity...
The interactions of proteins with polysaccharides play a key role in the microbial hydrolysis cellulose and xylan, most abundant organic molecules biosphere, are thus pivotal to recycling photosynthetically fixed carbon. Enzymes that attack these recalcitrant polymers have modular structure comprising catalytic modules non-catalytic carbohydrate-binding (CBMs). largest prokaryotic CBM family, CBM2, contains members bind (CBM2a) xylan (CBM2b), respectively. A possible explanation for...
Glycoside hydrolases that degrade plant cell walls have complex molecular architectures in which one or more catalytic modules are appended to noncatalytic carbohydrate-binding (CBMs). CBMs promote binding polysaccharides and potentiate enzymic hydrolysis. Although there diverse sequence-based families of xylan-binding CBMs, these modules, general, recognize both decorated unsubstituted forms the target polysaccharide, thus evolutionary rationale for this diversity is unclear. Using...
Glycosylation of macrolide antibiotics confers host cell immunity from endogenous and exogenous agents. The Streptomyces antibioticus glycosyltransferases, OleI OleD, glycosylate inactivate oleandomycin diverse macrolides including erythromycin, respectively. structure these enzyme-ligand complexes, in tandem with kinetic analysis site-directed variants, provide insight into the interaction their synthetic apparatus. Erythromycin binds to OleD 23S RNA its target ribosome same conformation...
Signaling across the membrane in response to extracellular stimuli is essential for survival of all cells. In bacteria, responses environmental changes are predominantly mediated by two-component systems, which typically composed a membrane-spanning sensor histidine kinase and cytoplasmic regulator. human gut symbiont Bacteroides thetaiotaomicron , hybrid systems key part bacterium’s ability sense degrade complex carbohydrates gut. Here, we identify activating ligand system, BT4663, controls...
Enzyme systems that attack the plant cell wall contain noncatalytic carbohydrate-binding modules (CBMs) mediate attachment to this composite structure and play a pivotal role in maximizing hydrolytic process. Although xyloglucan, which includes backbone of β-1,4-glucan decorated primarily with xylose residues, is key component wall, CBMs bind polymer have not been identified. Here we showed C-terminal domain modular <i>Clostridium thermocellum</i> enzyme <i>Ct</i>Cel9D-Cel44A (formerly known...