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研究领域

Bacterial oxygenases Bacteria that can grow using hydrocarbons as their sole source of carbon and energy produce oxygenases that have the ability to perform specific oxygenation of a wide range of hydrocarbons and chlorinated organic compounds, many of which are unreactive towards oxidation by chemical means. Bacterial oxygenases are thus potentially useful in bioremediation and, thanks to the remarkable stereo- and regio-selectivity that such enzymes can demonstrate, have potential applications in the synthesis of fine chemicals. Soluble methane monooxygenase (sMMO) from methane-oxidising bacteria naturally oxidises methane to methanol, which is the first step in biological oxidation of the potent greenhouse gas methane. It also co-oxidises a wide range of hydrocarbon and chlorinated hydrocarbon substrates. We are using mutagenesis-based methods to investigate and manipulate the very wide substrate range of sMMO and to investigate the mechanism of oxidation of the enzyme's kinetically unreactive substrate methane. This work is currently funded by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC) and is a collaboration with Professor J Colin Murrell at the University of East Anglia. We are also working with Professor John Lipscomb (University of Minnesota) to study reaction kinetics in sMMO. We are performing structure-function studies on alkene monooxygenase (AMO), which is produced by the alkene-oxidising bacterium Rhodococcus rhodochrous B-276 and can be used to produce high-value chiral epoxides. New expression systems for biocatalysts In addition to the expression systems that have already been developed for AMO and sMMO, work is also underway exploring the expression of stereoselective oxygenases in a bacterium that grows using methanol as its carbon and energy source in order to produce high-value biocatalysts using methanol as the feedstock. This project is in collaboration with Dr C Míguez and co-workers at the Biotechnology Research Institute, Montreal. Molecular environmental microbiology of the hospital ward environment We are applying molecular microbial ecology methods, including the polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) to study populations of microorganisms and resistance genes within the internal environment of hospital wards and other areas, as a new tool to study the role of the environment in hospital-acquired infections. This work is a collaboration with Dr Karen Stanley (Sheffield Hallam) and Mr Robert Kerry and Dr Robert Townsend (Sheffield Teaching Hospitals NHS Foundation Trust). It is funded by the Hospital Infection Society. Microbiological applications in materials science Research is underway into applications of bacteria within materials science, including inhibition of corrosion and biofouling and development of biosensors. This work is in collaboration with Professor Bob Akid at the University of Manchester. Work on development of a novel coating containing 'good' bacteria for inhibition of biofouling and corrosion is currently supported by the Engineering and Physical Sciences Research Council (EPSRC). Novel antimicrobial systems Work is under way to develop a new controlled-release coating for local delivery of antibiotics and other therapeutic agents for use on orthopedic prostheses and other surgical implants. This work is a collaboration with Professor Bob Akid at the University of Manchester and Dr Robert Townsend and Professor Ian Stockley (Sheffield Teaching Hospitals NHS trust). We are also working on isolation and characterisation of antimicrobial agents from natural products, including celery seeds. This work is a collaboration with Professor K D Rainsford(Sheffield Hallam University) and Dr Graham Stafford(School of Clinical Dentistry, University of Sheffield) and Dr Simon Jones(Department of Chemistry, University of Sheffield). Bioremediation of heavy metal and organic pollutants Microorganisms can be exploited to mitigate environmental pollution, by oxidising organic pollutants (such as hydrocarbons and chlorinated hydrocarbons) and by changing the speciation of heavy metals to make them less bioavailable. Work in collaboration with Dr Philip Gardiner investigates the potential of methane-oxidising and other environmental bacteria to remediate hexavalent chromium contamination. Other work is concerned with bioremediation of wastes from the petroleum industry.

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NICHOL, Tim, SMITH, Thomas, TOWNSEND, R, STOCKLEY, I and AKID, R (2016). Analysis of linezolid and tigecycline as candidates for local prophylaxis via antibiotic-loaded bone cement. The Journal of antimicrobial chemotherapy. (In Press) ESWAYAH, Abdurrahman, SMITH, Thomas and GARDINER, Philip (2016). Microbial transformations of selenium species of relevance to bioremediation. Applied and environmental microbiology, 82 (16), 4848-4859. DENG, Xiao, CAO, Shilin, LI, Ning, WU, Hong, SMITH, Thomas, ZONG, Minhua and LOU, Wenyong (2016). A magnetic biocatalyst based on mussel-inspired polydopamine and its acylation of dihydromyricetin. Chinese Journal of Catalysis, 37 (4), 584-595. SALIH, S., PASKINS, A., NICHOL, T., SMITH, Thomas and HAMER, A. (2015). The cement spacer with multiple indentations : increasing antibiotic elution using a cement spacer 'teabag'. The Bone & Joint Journal, 97-B (11), 1519-1524. EDUOK, Ubong, SULEIMAN, Rami, GITTENS, Jeanette, KHALED, Mazen, SMITH, Thomas J., AKID, Robert, EL ALI, Bassam and KHALIL, Amjad (2015). Anticorrosion/antifouling properties of bacterial spore-loaded sol-gel type coating for mild steel in saline marine condition: a case of thermophilic strain of Bacillus licheniformis. RSC Advances, 5 (114), 93818-93830. NICHOL, Tim, MURRELL, J. Colin and SMITH, Thomas J. (2015). Controlling the activities of the Diiron Centre in bacterial monooxygenases: lessons from mutagenesis and biodiversity. European Journal of Inorganic Chemistry, 2015 (21), 3419-3431.

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