Associate Professor Stephen Bell

Stephen Bell
Senior Lecturer
School of Physical Sciences
Faculty of Sciences

The screening, engineering and directed evolution of enzymes holds great promise for biotechnological applications. In the lab we study enzymes for biocatalysis and organic synthesis applications. The ultimate goal is to develop these systems as biocatalysts for clean, sustainable, low energy oxidation processes with applications in natural product synthesis (for example generation of valuable flavour and fragrance compounds) and then bioremediation of recalcitrant compounds such as aromatic hydrocarbons.

We engineer cytochrome P450 enzymes to alter their function and identify new enzymes from metabolically diverse bacteria which are capable of binding and oxidising a wide range of organic compounds. We identify new electron transfer partners (e.g. iron-sulphur ferredoxin proteins and flavoproteins) in order to improve the efficiency of the enzymes which is essential for scale-up of their activity. We develop whole cell oxidation systems, which enable the easy screening, scale-up and production of oxygenated organic products.

We are involved in collaborative work with other researchers to
1) to study the mechanism of action of these enzymes which is important in understanding drug metabolism and design
2) Determine the structure of the enzymes by X-ray crystallography and other techniques such as NMR and Mass Spectroscopy
3) Immobilise the enzymes on different solid state supports to enhance their stability and lifetime.

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Associate Professor Stephen Bell

The screening, engineering and directed evolution of enzymes holds great promise for biotechnological applications. In the lab we study enzymes for biocatalysis and organic synthesis applications. The ultimate goal is to develop these systems as biocatalysts for clean, sustainable, low energy oxidation processes with applications in natural product synthesis (for example generation of valuable flavour and fragrance compounds) and then bioremediation of recalcitrant compounds such as aromatic hydrocarbons.

We engineer cytochrome P450 enzymes to alter their function and identify new enzymes from metabolically diverse bacteria which are capable of binding and oxidising a wide range of organic compounds. We identify new electron transfer partners (e.g. iron-sulphur ferredoxin proteins and flavoproteins) in order to improve the efficiency of the enzymes which is essential for scale-up of their activity. We develop whole cell oxidation systems, which enable the easy screening, scale-up and production of oxygenated organic products.

We are involved in collaborative work with other researchers to
1) to study the mechanism of action of these enzymes which is important in understanding drug metabolism and design
2) Determine the structure of the enzymes by X-ray crystallography and other techniques such as NMR and Mass Spectroscopy
3) Immobilise the enzymes on different solid state supports to enhance their stability and lifetime.

Genome mining and protein engineering of cytochrome P450 enzymes for biocatalysis

The cytochrome P450 superfamily of haem iron monooxygenases is found in virtually all living organisms. They catalyse the oxidation of numerous endogenous and exogenous organic compounds and perform vital functions such as the biosynthesis of steroids and antibiotics and oxidative detoxification of xenobiotics. These monooxygenase enzymes catalyse the insertion of one atom of atmospheric oxygen into a carbon hydrogen bond.

R–H + 2H+ + 2e + O2  →  R–OH + H2O

The screening, engineering and directed evolution of cytochrome P450 enzymes for the oxidation of non-natural substrates holds great promise for biotechnological applications. In the lab we study these cytochrome P450 enzymes and their electron transfer partners for biocatalysis and organic synthesis applications. The ultimate goal is to develop these systems as biocatalysts for clean, sustainable, low energy oxidation processes in natural product synthesis and bioremediation of recalcitrant compounds.

We identify new enzymes from a wide range of bacteria and aim to work out their function and potential applications. This could range from

1) work with designing inhibitors for P450s which play an important role in pathogenic bacteria

2) P450s involved in the synthesis of important secondary metabolites in the bacteria.

We engineer cytochrome P450 enzymes to alter their function and identify new enzymes from metabolically diverse bacteria which are capable of binding and oxidising a wide range of organic compounds. For example we have recently isolated CYP enzymes that are capable of hydroxylating sesquiterpenoids, steroids, alkanes, polyaromatic hydrocarbons and substituted aromatics. We also identify new and engineer existing electron transfer partners (e.g. iron-sulphur ferredoxin proteins and flavoproteins) in order to improve the efficiency of the enzymes which is essential for scale-up of their activity. We also develop whole cell oxidation systems, which enable the easy screening, scale-up and production of oxygenated organic products. We aim to further optimise and scale-up these systems (in vitro and in vivo) using fermentor technology and bioprocess engineering to generate products on a large scale.

This work has led to the formation of a spin out company Oxford Biotrans (http://oxfordbiotrans.com/) which has been set up to use biocatalysis to generate compounds of use to the flavour and fragrance industry.

Students undertake a wider range of activities at the interface of Chemistry and Biochemistry including protein synthesis and engineering (molecular biology), analytical and organic chemistry techniques, enzyme assays structure function studies. Members of the group undertake crystallographic, electrochemical and EPR (electron paramagnetic resonance) studies of these cytochrome P450 enzymes  and their electron transfer partners at Adelaide and in collaboration with others. This provides gain a better understanding of different steps in the catalytic cycle and the protein-protein interactions in these systems.

The Australian Research Council are currently funding our research into P450 mechanism through a Discovery Project Grants. My research into isolating and understanding novel P450 electron transfer partners is funded through an ARC Future Fellowship.

My group currently consists of 5 PhD Students and 2 M. Phil Students.

Potential research students are directed to the Adelaide Graduate Centre for information on admissions, applications and scholarship

http://www.adelaide.edu.au/graduatecentre/admission/form.html

Questions regarding typical research projects can be directed to Dr Bell.

Appointments

Date Position Institution name
2017 Associate Professor and ARC Future Fellow University of Adelaide
2015 - 2016 Senior Lecturer and ARC Future Fellow University of Adelaide
2012 - 2014 Lecturer University of Adelaide

Awards and Achievements

Date Type Title Institution Name Amount
2016 Teaching Award OLT Citation for Outstanding Contributions to Student Learning University of Adelaide/Australian Government Department of Education and Training
2015 Fellowship ARC Future Fellowship University of Adelaide
2013 Achievement Founding Shareholder of Oxford Biotrans

Education

Date Institution name Country Title
University of Oxford United Kingdom BA and MA Chemistry (Oxon)
Oxford university United Kingdom DPhil

Journals

Year Citation
2017 Hall, E., Sarkar, M. & Bell, S. (2017). The selective oxidation of substituted aromatic hydrocarbons and the observation of uncoupling via redox cycling during naphthalene oxidation by the CYP101B1 system. Catalysis Science and Technology, 7, 7, 1537-1548.
10.1039/C7CY00088J
2017 Maddigan, N. & Bell, S. (2017). The self-sufficient CYP102 family enzyme, Krac9955, from Ktedonobacter racemifer DSM44963 acts as an alkyl- and alkyloxy-benzoic acid hydroxylase. Archives of Biochemistry and Biophysics, 615, 15-21.
10.1016/j.abb.2016.12.014
2017 Munday, S., Dezvarei, S., Lau, I. & Bell, S. (2017). Examination of selectivity in the oxidation of ortho- and meta-disubstituted benzenes by CYP102A1 (P450 Bm3) variants. ChemCatChem, 9, 13, 2512-2522.
10.1002/cctc.201700116
2017 Sarkar, M., Lee, J. & Bell, S. (2017). The Oxidation of Hydrophobic Aromatic Substrates by Using a Variant of the P450 Monooxygenase CYP101B1. ChemBioChem, 18, 21, 2119-2128.
10.1002/cbic.201700316
2016 Munday, S., Maddigan, N., Young, R. & Bell, S. (2016). Characterisation of two self-sufficient CYP102 family monooxygenases from Ktedonobacter racemifer DSM44963 which have new fatty acid alcohol product profiles. Biochimica et Biophysica Acta - General Subjects, 1860, 6, 1149-1162.
10.1016/j.bbagen.2016.01.023
2016 Bell, S., Hall, E., Sarkar, M. & Dasgupta, S. (2016). The Use of Directing Groups Enables the Selective and Efficient Biocatalytic Oxidation of Unactivated Adamantyl C-H Bonds. Chemistry Select, 1, 21, 6700-6707.
10.1002/slct.201601615
2016 Chao, R., De Voss, J. & Bell, S. (2016). The efficient and selective catalytic oxidation of para-substituted cinnamic acid derivatives by the cytochrome P450 monooxygenase, CYP199A4. RSC Advances, 6, 60, 55286-55297.
10.1039/c6ra11025h
2016 Coleman, T., Chao, R., De Voss, J. & Bell, S. (2016). The importance of the benzoic acid carboxylate moiety for substrate recognition by CYP199A4 from Rhodopseudomonas palustris HaA2. Biochimica et Biophysica Acta - Proteins and Proteomics, 1864, 6, 667-675.
10.1016/j.bbapap.2016.03.006
2016 Chao, R., Lau, I., De Voss, J. & Bell, S. (2016). Modification of an Enzyme Biocatalyst for the Efficient and Selective Oxidative Demethylation of para-Substituted Benzene Derivatives. ChemCatChem, 8, 23, 3626-3635.
10.1002/cctc.201600951
2016 Munday, S., Dezvarei, S. & Bell, S. (2016). Increasing the activity and efficiency of stereoselective oxidations by using decoy molecules in combination with rate-enhancing variants of P450Bm3. ChemCatChem, 8, 17, 2789-2796.
10.1002/cctc.201600551
2016 Stok, J. E., Hall, E. A., Stone, I. S. J., Noble, M. C., Wong, S. H., Bell, S. G. & De Voss, J. J. (2016). In vivo and in vitro hydroxylation of cineole and camphor by cytochromes P450CYP101A1, CYP101B1 and N242A CYP176A1. Journal of Molecular Catalysis B: Enzymatic, 128, 52-64.
10.1016/j.molcatb.2016.03.004
2016 Munday, S., Shoji, O., Watanabe, Y., Wong, L. & Bell, S. (2016). Improved oxidation of aromatic and aliphatic hydrocarbons using rate enhancing variants of P450Bm3 in combination with decoy molecules. Chemical Communications, 52, 5, 1036-1039.
10.1039/C5CC09247G
2016 Hall, E., Sarkar, M., Lee, J., Munday, S. & Bell, S. (2016). Improving the monooxygenase activity and the regio- and stereoselectivity of terpenoid hydroxylation using ester directing groups. ACS Catalysis, 6, 9, 6306-6317.
10.1021/acscatal.6b01882
2016 Liang, K., Coghlan, C., Bell, S., Doonan, C. & Falcaro, P. (2016). Enzyme encapsulation in zeolitic imidazolate frameworks: a comparison between controlled co-precipitation and biomimetic mineralisation. Chemical Communications, 52, 3, 473-476.
10.1039/C5CC07577G
2015 Coleman, T., Chao, R., Bruning, J., De Voss, J. & Bell, S. (2015). CYP199A4 catalyses the efficient demethylation and demethenylation of para-substituted benzoic acid derivatives. RSC Advances, 5, 64, 52007-52018.
10.1039/c5ra08730a
2015 Williamson, N., Huang, D., Bell, S. & Metha, G. (2015). Guided inquiry learning in an introductory chemistry course. International Journal of Innovation in Science and Mathematics Education, 23, 6, 34-51.
2015 Zhang, A., Zhang, T., Hall, E., Hutchinson, S., Cryle, M., Wong, L. ... Bell, S. (2015). The crystal structure of the versatile cytochrome P450 enzyme CYP109B1 from Bacillus subtilis. Molecular BioSystems, 11, 3, 869-881.
10.1039/c4mb00665h
2015 Hall, E. & Bell, S. (2015). The efficient and selective biocatalytic oxidation of norisoprenoid and aromatic substrates by CYP101B1 from Novosphingobium aromaticivorans DSM12444. RSC Advances, 5, 8, 5762-5773.
10.1039/c4ra14010a
2015 Liang, K., Ricco, R., Doherty, C. M., Styles, M. J., Bell, S., Kirby, N. ... Falcaro, P. (2015). Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules. Nature Communications, 6, 1-8.
10.1038/ncomms8240
2014 Bell, S., Spence, J., Liu, S., George, J. & Wong, L. (2014). Selective aliphatic carbon-hydrogen bond activation of protected alcohol substrates by cytochrome P450 enzymes. Organic and Biomolecular Chemistry, 12, 15, 2479-2488.
10.1039/c3ob42417k
2014 Zhang, T., Zhang, A., Bell, S., Wong, L. & Zhou, W. (2014). The structure of a novel electron-transfer ferredoxin from Rhodopseudomonas palustris HaA2 which contains a histidine residue in its iron-sulfur cluster-binding motif. Acta Crystallographica Section D: Biological Crystallography, D70, 5, 1453-1464.
10.1107/S139900471400474X
2013 Vohra, S., Musgaard, M., Bell, S., Wong, L., Zhou, W. & Biggin, P. (2013). The dynamics of camphor in the cytochrome P450 CYP101D2. Protein Science, 22, 9, 1218-1229.
10.1002/pro.2309
2013 Bell, S., Yang, W., Dale, A., Zhou, W. & Wong, L. (2013). Improving the affinity and activity of CYP101D2 for hydrophobic substrates. Applied Microbiology and Biotechnology, 97, 9, 3979-3990.
10.1007/s00253-012-4278-7
2013 Bell, S., French, L., Rees, N., Cheng, S., Preston, G. & Wong, L. (2013). A phthalate family oxygenase reductase supports terpene alcohol oxidation by CYP238A1 from Pseudomonas putida KT2440. Biotechnology and Applied Biochemistry, 60, 1, 9-17.
10.1002/bab.1084
2012 Bell, S., Yang, W., Yorke, J., Zhou, W., Wang, H., Harmer, J. ... Wong, L. (2012). Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: an aromatic hydrocarbon-binding P450 enzyme. Acta Crystallographica Section D-Biological Crystallography, 68, 3, 277-291.
10.1107/S090744491200145X
2012 Bell, S., Yang, W., Tan, A., Zhou, R., Johnson, E., Zhang, A. ... Wong, L. (2012). The crystal structures of 4-methoxybenzoate bound CYP199A2 and CYP199A4: structural changes on substrate binding and the identification of an anion binding site. Dalton Transactions (Print Edition), 41, 28, 8703-8714.
10.1039/C2DT30783A
2012 Bell, S., Zhou, R., Yang, W., Tan, A., Gentleman, A., Wong, L. & Zhou, W. (2012). Investigation of the substrate range of CYP199A4: modification of the partition between hydroxylation and desaturation activities by substrate and protein engineering. Chemistry-A European Journal, 18, 52, 16677-16688.
10.1002/chem.201202776
2012 Whitehouse, C., Bell, S. & Wong, L. (2012). P450BM3 (CYP102A1): connecting the dots. Chemical Society Reviews, 41, 3, 1218-1260.
10.1039/C1CS15192D
2012 Bell, S., McMillan, J., Yorke, J., Kavanagh, E., Johnson, E. & Wong, L. (2012). Tailoring an alien ferredoxin to support native-like P450 monooxygenase activity. Chemical Communications, 48, 95, 11692-11694.
10.1039/c2cc35968e
2012 Abdalla, J., Bowen, A., Bell, S., Wong, L., Timmel, C. & Harmer, J. (2012). Characterisation of the paramagnetic [2Fe-2S]⁺ centre in palustrisredoxin-B (PuxB) from Rhodopseudomonas palustris. Physical Chemistry Chemical Physics, 14, 18, 6526-6537.
10.1039/C2CP24112A
2011 Whitehouse, C., Rees, N., Bell, S. & Wong, L. (2011). Dearomatisation of xylene by P450BM3 (CYP102A1). Chemistry-A European Journal, 17, 24, 6862-6868.
10.1002/chem.201002465
2011 Zhou, R., Huang, C., Zhang, A., Bell, S., Zhou, W. & Wong, L. (2011). Crystallization and Preliminary X-ray analysis of CYP153C1 from Novosphingobium aromaticivorans DSM12444. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online, 67, 8, 964-967.
10.1107/S174430911102464X
2011 Whitehouse, C., Yang, W., Yorke, J., Tufton, H., Ogilvie, L., Bell, S. ... Wong, L. (2011). Structure, electronic properties and catalytic behaviour of an activity-enhancing CYP102A1 (P450BM3) variant. Dalton Transactions (Print Edition), 40, 40, 10383-10396.
10.1039/C1DT10098J
2011 Yang, W., Bell, S., Wang, H., Zhou, W., Bartlam, M., Wong, L. & Rao, Z. (2011). The structure of CYP101D2 unveils a potential path for substrate entry into the active site. Biochemical Journal, 433, 1, 85-93.
10.1042/BJ20101017
2011 Rowlatt, B., Yorke, J., Strong, A., Whitehouse, C., Bell, S. & Wong, L. (2011). Chain length-dependent cooperativity in fatty acid binding and oxidation by cytochrome P450BM3 (CYP102A1). Protein & Cell, 2, 8, 656-671.
10.1007/s13238-011-1082-6
2011 Ma, M., Bell, S., Yang, W., Hao, Y., Rees, N., Bartlam, M. ... Rao, Z. (2011). Structural analysis of CYP101C1 from Novosphingobium aromaticivorans DSM12444. ChemBioChem, 12, 1, 88-99.
10.1002/cbic.201000537
2010 Bell, S., Xu, F., Johnson, E., Forward, I., Bartlam, M., Rao, Z. & Wong, L. (2010). Protein recognition in ferredoxin-P450 electron transfer in the class I CYP199A2 system from Rhodopseudomonas palustris. Journal of Biological Inorganic Chemistry, 15, 3, 315-328.
10.1007/s00775-009-0604-7
2010 Bell, S., Tan, A., Johnson, E. & Wong, L. (2010). Selective oxidative demethylation of veratric acid to vanillic acid by CYP199A4 from Rhodopseudomonas palustris HaA2. Molecular BioSystems, 6, 1, 206-214.
10.1039/B913487E
2010 Bell, S., Dale, A., Rees, N. & Wong, L. (2010). A cytochrome P450 class I electron transfer system from Novosphingobium aromaticivorans. Applied Microbiology and Biotechnology, 86, 1, 163-175.
10.1007/s00253-009-2234-y
2010 Feng, X., Bell, S., Ying, P., Johnson, E., Bartlam, M., Rao, Z. & Luet-Lok, W. (2010). Erratum: Crystal structure of a ferredoxin reductase for the CYP199A2 system from Rhodopseudomonas palustris (Proteins: Structure, Function and Bioformatics (2009) 77 (867-880)). Proteins: Structure, Function and Bioinformatics, 78, 2, 501-.
10.1002/prot.22627
2010 Yang, W., Bell, S., Wang, H., Zhou, W., Hoskins, N., Dale, A. ... Rao, Z. (2010). Molecular characterization of a class I P450 electron transfer system from Novosphingobium aromaticivorans DSM12444. Journal of Biological Chemistry, 285, 35, 27372-27384.
10.1074/jbc.M110.118349
2010 Whitehouse, C., Yang, W., Yorke, J., Rowlatt, B., Strong, A., Blanford, C. ... Rao, Z. (2010). Structural basis for the properties of two single-site proline mutants of CYP102A1 (P450BM3). ChemBioChem, 11, 18, 2549-2556.
10.1002/cbic.201000421
2010 Cryle, M., Bell, S. & Schlichting, I. (2010). Structural and Biochemical Characterization of the Cytochrome P450 CypX (CYP134A1) from Bacillus subtilis: A Cyclo-l-leucyl-l-leucyl Dipeptide Oxidase. Biochemistry, 49, 34, 7282-7296.
10.1021/bi100910y
2009 Whitehouse, C., Bell, S., Yang, W., Yorke, J., Blanford, C., Strong, A. ... Wong, L. (2009). A highly active single-mutation variant of P450BM3 (CYP102A1). ChemBioChem, 10, 10, 1654-1656.
10.1002/cbic.200900279
2009 Xu, F., Bell, S., Peng, Y., Johnson, E., Bartlam, M., Rao, Z. & Wong, L. (2009). Crystal structure of a ferredoxin reductase for the CYP199A2 system from Rhodopseudomonas palustris. Proteins-Structure Function and Genetics, 77, 4, 867-880.
10.1002/prot.22510
2009 Bell, S. & Vallee, B. (2009). The Metallothionein/Thionein System: an oxidoreductive metabolic zinc link. ChemBioChem, 10, 1, 55-62.
10.1002/cbic.200800511
2009 Holland, J., Giansiracusa, J., Bell, S., Wong, L. & Dilworth, J. (2009). In vitro kinetic studies on the mechanism of oxygen-dependent cellular uptake of copper radiopharmaceuticals. Physics in Medicine and Biology, 54, 7, 2103-2119.
10.1088/0031-9155/54/7/017
2009 Hong, C., Bell, S., Yang, W., Wang, H., Hao, Y., Li, X. ... Wong, L. (2009). Purification, crystallization and preliminary X-ray analysis of cytochrome P450 219A1 from Novosphingobium aromaticivorans DSM 12444. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online, 65, 4, 364-367.
10.1107/S1744309109005648
2009 Lovett, J., Bowen, A., Timmel, C., Jones, M., Dilworth, J., Caprotti, D. ... Harmer, J. (2009). Structural information from orientationally selective DEER spectroscopy. Physical Chemistry Chemical Physics, 11, 31, 6840-6848.
10.1039/B907010A
2008 Whitehouse, C., Bell, S. & Wong, L. (2008). Desaturation of alkylbenzenes by Cytochrome P450BM3 (CYP102A1). Chemistry-A European Journal, 14, 35, 10905-10908.
10.1002/chem.200801927
2008 Guo, D., Xu, F., Bell, S., Pang, X., Bartlam, M. & Wong, L. (2008). Purification, crystallization and preliminary crystallographic analysis of CYP195A2, a P450 enzyme from Rhodopseudomonas palustris. Protein and Peptide Letters, 15, 4, 423-426.
10.2174/092986608784246470
2008 Bell, S., Xu, F., Forward, I., Bartlam, M., Rao, Z. & Wong, L. (2008). Crystal structure of CYP199A2, a para-substituted benzoic acid oxidizing cytochrome P450 from Rhodopseudomonas palustris. Journal of Molecular Biology, 383, 3, 561-574.
10.1016/j.jmb.2008.08.033
2008 Whitehouse, C., Bell, S., Tufton, H., Kenny, R., Ogilvie, L. & Wong, L. (2008). Evolved CYP102A1 (P450BM3) variants oxidise a range of non-natural substrates and offer new selectivity options. Chemical Communications, 28, 8, 966-968.
10.1039/B718124H
2007 Peng, Y., Xu, F., Bell, S., Wong, L. & Rao, Z. (2007). Crystallization and preliminary X-ray diffraction studies of a ferredoxin reductase from Rhodopseudomonas palustris CGA009. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online, 63, 5, 422-425.
10.1107/S1744309107017411
2007 Xu, F., Bell, S., Rao, Z. & Wong, L. (2007). Structure-activity correlations in pentachlorobenzene oxidation by engineered cytochrome P450cam. Protein Engineering Design and Selection, 20, 10, 473-480.
10.1093/protein/gzm028
2007 Pang, X., Xu, F., Bell, S., Guo, D., Wong, L. & Rao, Z. (2007). Purification, crystallization and preliminary crystallographic analysis of cytochrome P450 203A1 from Rhodopseudomonas palustris. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online, 63, 4, 342-345.
10.1107/S1744309107012705
2007 Bell, S. & Wong, L. (2007). P450 enzymes from the bacterium Novosphingobium aromaticivorans. Biochemical and Biophysical Research Communications, 360, 3, 666-672.
10.1016/j.bbrc.2007.06.119
2007 Fleming, B., Bell, S., Wong, L. L. & Bond, A. (2007). The electrochemistry of a heme-containing enzyme, CYP199A2, adsorbed directly onto a pyrolytic graphite electrode. Journal of Electroanalytical Chemistry, 611, 1-2, 149-154.
10.1016/j.jelechem.2007.08.016
2006 Bell, S., Hoskins, N., Xu, F., Caprotti, D., Rao, Z. & Wong, L. (2006). Cytochrome P450 enzymes from the metabolically diverse bacterium Rhodopseudomonas palustris. Biochemical and Biophysical Research Communications, 342, 1, 191-196.
10.1016/j.bbrc.2006.01.133
2005 Fleming, B., Zhang, J., Bond, A., Bell, S. & Wong, L. (2005). Separation of electron-transfer and coupled chemical reaction components of biocatalytic processes using Fourier transform ac voltammetry. Analytical Chemistry, 77, 11, 3502-3510.
10.1021/ac048151y
2005 Xu, F., Bell, S., Lednik, J., Insley, A., Rao, Z. & Wong, L. (2005). The heme monooxygenase cytochrome P450(cam) can be engineered to oxidize ethane to ethanol. Angewandte Chemie International Edition, 44, 26, 4029-4032.
10.1002/anie.200462630
2005 Sowden, R., Yasmin, S., Rees, N., Bell, S. & Wong, L. (2005). Biotransformation of the sesquiterpene (+)-valencene by cytochrome P450cam and P450BM-3. Organic and Biomolecular Chemistry, 3, 1, 57-64.
10.1039/b413068e
2003 Fleming, B., Tian, Y., Bell, S., Wong, L., Urlacher, V. & Allen O Hill, H. (2003). Redox properties of cytochrome P450BM3 measured by direct methods. European Journal of Biochemistry, 270, 20, 4082-4088.
10.1046/j.1432-1033.2003.03799.x
2003 Bell, S., Chen, X., Sowden, R., Xu, F., Williams, J., Wong, L. & Rao, Z. (2003). Molecular recognition in (+)-α-pinene oxidation by cytochrome P450cam. Journal of the American Chemical Society, 125, 3, 705-714.
10.1021/ja028460a
2003 Bell, S., Chen, X., Xu, F., Rao, Z. & Wong, L. (2003). Engineering substrate recognition in catalysis by cytochrome P450cam. Biochemical Society Transactions, 31, 3, 558-562.
10.1042/BST0310558
2003 Bell, S., Orton, E., Boyd, H., Stevenson, J., Riddle, A., Campbell, S. & Wong, L. (2003). Engineering cytochrome P450cam into an alkane hydroxylase. Dalton Transactions, 11, 2133-2140.
10.1039/b300869j
2003 Bentley, E., Astier, Y., Ji, W., Bell, S., Wong, L. & Hill, H. (2003). The electrochemistry and scanning tunnelling microscopy of the flavoprotein putidaredoxin reductase on alkanethiol-modified gold. Inorganica Chimica Acta, 356, 343-348.
10.1016/S0020-1693(03)00251-2
2002 Bell, S., Stevenson, J., Boyd, H., Campbell, S., Riddle, A., Orton, E. & Wong, L. (2002). Butane and propane oxidation by engineered cytochrome P450cam. Chemical Communications, 5, 490-491.
10.1039/b110957j
2002 Chen, X., Christopher, A., Jones, J., Bell, S., Guo, Q., Xu, F. ... Wong, L. (2002). Crystal structure of the F87W/Y96F/V247L mutant of cytochrome P-450cam with 1,3,5-trichlorobenzene bound and further protein engineering for the oxidation of pentachlorobenzene and hexachlorobenzene. Journal of Biological Chemistry, 277, 40, 37519-37526.
10.1074/jbc.M203762200
2001 Bell, S., Harford-Cross, C. & Wong, L. (2001). Engineering the CYP101 system for in vivo oxidation of unnatural substrates. Protein Engineering, 14, 10, 797-802.
10.1093/protein/14.10.797
2001 Bell, S., Sowden, R. & Wong, L. (2001). Engineering the haem monooxygenase cytochrome P450cam for monoterpene oxidation. Chemical Communications, 7, 635-636.
10.1039/b100290m
1997 Bell, S., Rouch, D. & Wong, L. (1997). Selective aliphatic and aromatic carbon-hydrogen bond activation catalysed by mutants of cytochrome p450(cam). Journal of Molecular Catalysis - B Enzymatic, 3, 6, 293-302.
10.1016/S1381-1177(97)00009-X
1996 England, P., Rouch, D., Westlake, A., Bell, S., Nickerson, D., Webberley, M. ... Wong, L. (1996). Aliphatic vs. aromatic C-H bond activation of phenylcyclohexane catalysed by cytochrome P450cam. Chemical Communications, 3, 357-358.
10.1039/cc9960000357

Book Chapters

Year Citation
2007 Urlacher, V., Bell, S. & Wong, L. L. (2007). The bacterial cytochrome P450 monooxygenases: P450cam and P450BM-3. In R. D. Schmid & V. B. Urlacher (Eds.), Modern Biooxidation: Enzymes, Reactions and Applications (pp. 99-122). Federal Republic of Germany: Wiley.
10.1002/97835276110
2007 Bell, S., Hoskins, N., Whitehouse, C. & Wong, L. L. (2007). Design and engineering of cytochrome P450 systems. In A. Sigel, H. Sigel & R. K. O. Sigel (Eds.), The Ubiquitous Roles of Cytochrome P450 Proteins: Metal Ions in Life Sciences (Volume 3) (pp. 437-476). West Sussex, England: Wiley.
10.1002/9780470028155.ch14

Conference Papers

Year Citation
2017 Wong, S., Bell, S. & De Voss, J. (2017). P450 catalysed dehydrogenation.
10.1515/pac-2016-1216
2010 Wong, L. L., Whitehouse, C. J., Yang, W., Yorke, J. A., Blanford, C. F., Bell, S. G. ... Rao, Z. (2010). Engineering P450s by Rational Design. 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics(ISSX). Istanbul, TURKEY.

Conference Items

Year Citation
2012 Williamson, N. M., Metha, G. F., Huang, D. M. & Bell, S. G. (2012). Development of POGIL-Style Organic Chemistry Activities. Australian Conference on Science and Mathematics Education. Sydney.

Patents

Year Citation
2009 Wong, L. L., Bell, S. & Whitehouse, C.; (2009); Mutant Enzymes;

The Australian Research Council are currently funding our research into P450 mechanism through Discovery Project Grants and a Future Fellowship

ARC Discovery Project (2017-2019) DP170103531 Metal-organic Frameworks at the Biointerface (Christian Doonan. Chris Sumby, Stephen Bell, Paolo Falcaro)

This research will yield a detailed understanding of the chemistry that governs the crystallisation of Metal-organic Frameworks around functional biomacromolecules and explore the potential applications of these novel biocomposites. Functional biomacromolecules, such as proteins, show great promise for application to areas of significant commercial and social interest, like biotechnology and Industrial biocatalysis. The research will make significant advances toward the widespread commercial application of biocatalysts and biosensors by developing unique MOF-encapsulated biocatalytic platform materials that will allow inherently fragile biomacromolecules to retain activity in conditions typically required for industrial processes.

My research into isolating and understanding novel P450 electron transfer partners is funded through an ARC Future Fellowship (FT140100355).

ARC Future Fellow, (2014-2018) FT140100355 .

Enzyme catalysed oxidation reactions are key players in the production of naturally occurring biologically active molecules. These processes are tightly regulated by their electron transfer partners. This project will characterise new electron transfer ferredoxin proteins from a metabolically diverse bacterium.  The outcomes will advance our understanding of electron transfer, a fundamental process. This will allow strategies to combat human and plant pathogens and unlock the potential of these systems as biocatalysts for the green chemical synthesis of complex and valuable chemicals.

ARC Discovery Project (2014-2016) DP140103229 (James De Voss, Stephen Bell, Mark Bartlam)

Cytochromes P450 are enzymes that play key roles in drug metabolism and biosynthesis. P450s often catalyse hydroxylation but also carry out important transformations such as dehydrogenation or carbon-carbon bond cleavage. Such reactions are pivotal in many biological pathways. This work will elucidate the mechanism of these transformations and the factors that facilitate their occurrence. This will mainly entail the synthesis of small organic mechanistic probes and determining the structure and stereochemistry of the product of enzymic oxidation. Understanding these mechanisms will allow us to predict when such reactions will occur, enabling their utilisation in for example drug design in the avoidance of the formation of toxic metabolites.

I have taught a broad range of courses across all Levels of Chemistry with a focus on Inorganic Chemistry.

Currently whilst on a Future Fellowship I am teaching two level III course

Chem III Inorganic Reaction Mechanisms - with a focus on the reaction kinetics of ligand exchange in metal complexes and how this can be applied to design of metal complexes which can be used in biology and medicine.

Medicinal and Biological Chemistry III - Electron transfer - focus on electron transfer in Chemistry and Biology. Understanding the mechanism, significance and roles of electron transfer in metal-ligand complexes and biological systems. How biological systems have been optimised to regulate electron transfer processes which are critical to life.

My group currently consists of 5 PhD Students and 2 M. Phil Students.

All former students are employed in a variety of sectors including Industry and teaching.

Potential research students are directed to the Adelaide Graduate Centre for information on admissions, applications and scholarship

http://www.adelaide.edu.au/graduatecentre/admission/form.html

Questions regarding typical research projects can be directed to Dr Bell.

Committee Memberships

Date Role Committee Institution Country
2013 - ongoing Member Steering committee of the Adelaide Integrated Bioscience Laboratories Australia

Editorial Boards

Date Role Editorial Board Name Country
2016 - ongoing Member Scientific Reports
Position
Senior Lecturer
Phone
83134822
Fax
8313 4380
Campus
North Terrace
Building
Badger
Room Number
G 22
Org Unit
Chemistry

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