Associate Professor Stephen Bell

Associate Professor Stephen Bell
 Position Senior Lecturer
 Org Unit Chemistry
 Email stephen.bell@adelaide.edu.au
 Telephone +61 8 8313 4822
 Location Floor/Room G 22 ,  Badger ,   North Terrace
  • Biography/ Background

    BA Chemistry (Oxon), 1995

    MA (Oxon),

    DPhil Chemistry University of Oxford, 2000 (The use of active site mutants of cytochrome P450cam in chemical synthesis)

    Post doctoral Research Assistant, University of Oxford 2000-2004 and 2006-2009

    Junior Research Fellow, The Queen's College Oxford, 2007-2011

    Inorganic Chemistry Lecturer, Brasenose College Oxford, 2008-2011

    Lecturer Inorganic Chemistry, University of Adelaide 2012-2014

    Senior Lecturer and ARC Future Fellow, University of Adelaide 2015 to date

  • Teaching Interests

    Inorganic Chemistry

    Biological Chemistry, Molecular Biology, Enzymology

     

    I teach (or have taught) on the following courses

    Foundations of Chemistry IB: Redox chemistry and Periodicity

    Foundations of Chemistry IA: Molecular Behaviour

    Environmental and Analytical Chemistry II: Separation Techniques (Chromatography and MS)

    Chem II B: Applications of Symmetry

    Advanced Synthetic Methods: Metals in Synthesis

    Medicinal and Biological III: Electron transfer in Biology

    Chem III: Inorganic Reaction Mechanism

     

  • Research Interests

    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 

    to

    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 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.

    With collaborators we are undertaking crystallographic, electrochemical and EPR (electron paramagnetic resonance) studies of these cytochrome P450 enzymes and their electron transfer partners in order to 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 Grant (DP140103229) with Prof. James de Voss at the University of Queensland. My research into isolating and understanding novel P450 electron transfer partners is funded through an ARC Future Fellowship (FT140100355).

    I also have a research interest in the role of zinc and copper binding metallothioneins in neurodegenerative diseases.

    My group currently consists of 2 PhD Students, 4 M. Phil Students and 2 Honours 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.

  • Publications

     

    a full list of publications can be found here

    http://www.researcherid.com/rid/E-8222-2011

    or

    http://scholar.google.com.au/citations?user=htSzKIEAAAAJ&hl=en

     

    Selected publications

     

    Zhang, A., Zhang, T., Hall, E. A., Hutchinson, S., Cryle, M. J., Wong, L. -L., . . . Bell, S. G. (2015). The crystal structure of the versatile cytochrome P450 enzyme CYP109B1 from Bacillus subtilis. Molecular BioSystems, 11(3), 869-881. doi:10.1039/c4mb00665h

    Hall, E. A., & Bell, S. G. (2015). The efficient and selective biocatalytic oxidation of norisoprenoid and aromatic substrates by CYP101B1 from Novosphingobium aromaticivorans DSM12444. RSC Advances, 5(8), 5762-5773. doi:10.1039/c4ra14010a

    Bell, S.G., Spence, J., Liu, S., George, J., & Wong, L. L. (2014). Selective aliphatic carbon-hydrogen bond activation of protected alcohol substrates by cytochrome P450 enzymes. Organic and Biomolecular Chemistry, 12(15), 2479-2488. doi:10.1039/c3ob42417k

    Zhang, T., Zhang, A., Bell, S. G., Wong, L. 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. doi:10.1107/S139900471400474X

    Bell, S. G., Yang, W., Dale, A., Zhou, W., & Wong. (2013). Improving the affinity and activity of CYP101D2 for hydrophobic substrates. Applied Microbiology and Biotechnology, 97(9), 3979-3990. doi:10.1007/s00253-012-4278-7

    Bell, S., French, L., Rees, N., Cheng, S., Preston, G., & Wong, L. 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. doi:10.1002/bab.1084

    Bell, S., Yang, W., Dale, A., Zhou, W., & Wong, L. L. (2013). Improving the affinity and activity of CYP101D2 for hydrophobic substrates. Applied Microbiology and Biotechnology, 97(9), 3979-3990. doi:10.1007/s00253-012-4278-7

    Vohra, S., Musgaard, M., Bell, S., Wong, L. L., Zhou, W., & Biggin, P. (2013). The dynamics of camphor in the cytochrome P450 CYP101D2. Protein Science, 22(9), 1218-1229. doi:10.1002/pro.2309

    Abdalla, J., Bowen, A., Bell, S., Wong, L. 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. doi:10.1039/C2CP24112A

    Bell, S., Zhou, R., Yang, W., Tan, A., Gentleman, A., Wong, L. 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. doi:10.1002/chem.201202776

    Whitehouse, C., Bell, S., & Wong, L. L. (2012). P450BM3 (CYP102A1): connecting the dots. Chemical Society Reviews, 41(3), 1218-1260. doi:10.1039/C1CS15192D

    Bell, S., Yang, W., Yorke, J., Zhou, W., Wang, H., Harmer, J., . . . Wong, L. 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. doi:10.1107/S090744491200145X

    Bell, S., McMillan, J., Yorke, J., Kavanagh, E., Johnson, E., & Wong, L. L. (2012). Tailoring an alien ferredoxin to support native-like P450 monooxygenase activity. Chemical Communications, 48(95), 11692-11694. doi:10.1039/c2cc35968e

    Bell, S., Yang, W., Tan, A., Zhou, R., Johnson, E., Zhang, A., . . . Wong, L. 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. doi:10.1039/C2DT30783A

    Zhou, R., Huang, C., Zhang, A., Bell, S., Zhou, W., & Wong, L. 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. doi:10.1107/S174430911102464X

    Whitehouse, C., Rees, N., Bell, S., & Wong, L. L. (2011). Dearomatisation of xylene by P450BM3 (CYP102A1). Chemistry-A European Journal, 17(24), 6862-6868. doi:10.1002/chem.201002465

    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. doi:10.1002/cbic.201000537

    Whitehouse, C., Yang, W., Yorke, J., Tufton, H., Ogilvie, L., Bell, S., . . . Wong, L. L. (2011). Structure, electronic properties and catalytic behaviour of an activity-enhancing CYP102A1 (P450BM3) variant. Dalton Transactions (Print Edition), 40(40), 10383-10396. doi:10.1039/C1DT10098J

    Yang, W., Bell, S., Wang, H., Zhou, W., Bartlam, M., Wong, L. 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. doi:10.1042/BJ20101017

    Bell, S., Dale, A., Rees, N., & Wong, L. L. (2010). A cytochrome P450 class I electron transfer system from Novosphingobium aromaticivorans. Applied Microbiology and Biotechnology, 86(1), 163-175. doi:10.1007/s00253-009-2234-y

    Feng, X., Bell, S. G., Ying, P., Johnson, E. O. D., 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. doi:10.1002/prot.22627

    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. doi:10.1074/jbc.M110.118349

    Bell, S., Xu, F., Johnson, E., Forward, I., Bartlam, M., Rao, Z., . . . Wong, L. 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. doi:10.1007/s00775-009-0604-7

    Bell, S., Tan, A., Johnson, E., & Wong, L. L. (2010). Selective oxidative demethylation of veratric acid to vanillic acid by CYP199A4 from Rhodopseudomonas palustris HaA2. Molecular BioSystems, 6(1), 206-214. doi:10.1039/B913487E

    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. doi:10.1002/cbic.201000421

    Whitehouse, C., Bell, S., Yang, W., Yorke, J., Blanford, C., Strong, A., . . . Wong, L. L. (2009). A highly active single-mutation variant of P450BM3 (CYP102A1). ChemBioChem, 10(10), 1654-1656. doi:10.1002/cbic.200900279

    Xu, F., Bell, S., Peng, Y., Johnson, E., Bartlam, M., Rao, Z., . . . Wong, L. L. (2009). Crystal structure of a ferredoxin reductase for the CYP199A2 system from Rhodopseudomonas palustris. Proteins-Structure Function and Genetics, 77(4), 867-880. doi:10.1002/prot.22510

     

    Hong, C., Bell, S., Yang, W., Wang, H., Hao, Y., Li, X., . . . Wong, L. 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. doi:10.1107/S1744309109005648

    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. doi:10.1039/B907010A

    Bell, S., & Vallee, B. (2009). The Metallothionein/Thionein System: an oxidoreductive metabolic zinc link. ChemBioChem, 10(1), 55-62. doi:10.1002/cbic.200800511

    Bell, S., Xu, F., Forward, I., Bartlam, M., Rao, Z., & Wong, L. 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. doi:10.1016/j.jmb.2008.08.033

    Whitehouse, C., Bell, S., & Wong, L. L. (2008). Desaturation of alkylbenzenes by Cytochrome P450BM3 (CYP102A1). Chemistry-A European Journal, 14(35), 10905-10908. doi:10.1002/chem.200801927

    Whitehouse, C., Bell, S., Tufton, H., Kenny, R., Ogilvie, L., & Wong, L. L. (2008). Evolved CYP102A1 (P450BM3) variants oxidise a range of non-natural substrates and offer new selectivity options. Chemical Communications, 28(8), 966-968. doi:10.1039/B718124H

    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) (Vol. 3, pp. 437-476). West Sussex, England: Wiley. doi:10.1002/9780470028155.ch14

    Bell, S., & Wong, L. L. (2007). P450 enzymes from the bacterium Novosphingobium aromaticivorans. Biochemical and Biophysical Research Communications, 360(3), 666-672. doi:10.1016/j.bbrc.2007.06.119

    Xu, F., Bell, S., Rao, Z., & Wong, L. L. (2007). Structure-activity correlations in pentachlorobenzene oxidation by engineered cytochrome P450cam. Protein Engineering Design and Selection, 20(10), 473-480. doi:10.1093/protein/gzm028

    Bell, S. G., Hoskins, N., Xu, F., Caprotti, D., Rao, Z., & Wong, L. L. (2006). Cytochrome P450 enzymes from the metabolically diverse bacterium Rhodopseudomonas palustris. Biochemical and Biophysical Research Communications, 342(1), 191-196. doi:10.1016/j.bbrc.2006.01.133

    Sowden, R. J., Yasmin, S., Rees, N. H., Bell, S. G., & Wong, L. L. (2005). Biotransformation of the sesquiterpene (+)-valencene by cytochrome P450cam and P450BM-3
    . Organic and Biomolecular Chemistry, 3(1), 57-64. doi:10.1039/b413068e

    Xu, F., Bell, S. G., Lednik, J., Insley, A., Rao, Z. H., & Wong, L. L. (2005). The heme monooxygenase cytochrome P450(cam) can be engineered to oxidize ethane to ethanol. Angewandte Chemie International Edition, 44(26), 4029-4032. doi:10.1002/anie.200462630

    Bell, S. G., Chen, X., Xu, F., Rao, Z., & Wong, L. L. (2003). Engineering substrate recognition in catalysis by cytochrome P450cam. Biochemical Society Transactions, 31(3), 558-562. doi:10.1042/BST0310558

    Bell, S. G., Chen, X., Sowden, R. J., Xu, F., Williams, J. N., Wong, L. L., . . . Rao, Z. (2003). Molecular recognition in (+)-α-pinene oxidation by cytochrome P450cam
    . Journal of the American Chemical Society, 125(3), 705-714. doi:10.1021/ja028460a

    Bell, S. G., Orton, E., Boyd, H., Stevenson, J. A., Riddle, A., Campbell, S., . . . Wong, L. L. (2003). Engineering cytochrome P450cam into an alkane hydroxylase. Dalton Transactions, (11), 2133-2140. doi:10.1039/b300869j

    Chen, X., Christopher, A., Jones, J. P., Bell, S. G., Guo, Q., Xu, F., . . . Wong, L. 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. doi:10.1074/jbc.M203762200

    Bell, S. G., Stevenson, J. A., Boyd, H. D., Campbell, S., Riddle, A. D., Orton, E. L., . . . Wong, L. L. (2002). Butane and propane oxidation by engineered cytochrome P450cam
    . Chemical Communications, (5), 490-491. doi:10.1039/b110957j

    Bell, S. G., Harford-Cross, C. F., & Wong, L. L. (2001). Engineering the CYP101 system for in vivo oxidation of unnatural substrates. Protein Engineering, 14(10), 797-802. doi:10.1093/protein/14.10.797

    Bell, S. G., Sowden, R. J., & Wong, L. L. (2001). Engineering the haem monooxygenase cytochrome P450cam for monoterpene oxidation. Chemical Communications, (7), 635-636. doi:10.1039/b100290m

     

The information in this directory is provided to support the academic, administrative and business activities of the University of Adelaide. To facilitate these activities, entries in the University Phone Directory are not limited to University employees. The use of information provided here for any other purpose, including the sending of unsolicited commercial material via email or any other electronic format, is strictly prohibited. The University reserves the right to recover all costs incurred in the event of breach of this policy.

Entry last updated: Friday, 17 Mar 2017

To link to this page, please use the following URL:  https://www.adelaide.edu.au/directory/stephen.bell