Dr Stephen Bell

Biography/ Background

BA Chemistry (Oxon), 1995

MA (Oxon),

DPhil Chemistry University of Oxford, 2000 (The use of active site mutants of cytochrome P450_cam 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 January 2012 to date

Teaching Interests

Inorganic Chemistry

Biological Chemistry, Molecular Biology, Enzymology

 

I teach on the following courses

Foundations of Chemistry IB: Redox chemistry and Periodicity

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

Chem II B: Applications of Symmetry

Advanced Synthetic Methods: Metals in Synthesi

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.

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

 

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

 

Selected publications

Bell, S.G., Zhou, R., Yang, W., Tan, A.B.H., Gentleman, A.S., Wong, L.-L. and Zhou, W. (2012) Investigation of the substrate range of CYP199A4: modification of the partition between hydroxylation and desaturation activities by substrate and protein engineering. Chem Eur J, DOI: 10.1002/chem.201202776 PDF

 

Bell,S.G., McMillan, J.H.C., Yorke,J.A. Johnson, E.O.D.  Kavanagh, E. and Wong, L.-L. (2012) Tailoring an alien ferredoxin to support native-like P450 monooxygenase activity. Chem Commun, 48, 11692-11694 PDF

 

Bell S.G., Yang W., Dale A., Zhou W. and Wong L.-L. (2012) Improving the afffinity and activity of CYP101D2 for hydrophobic substrates. Appl Microbiol Biotechnol. Accepted in press DOI 10.1007/s00253-012-4278-7 PDF

 

Bell, S.G., Yang, W., Tan, A.B.H., Zhou, R., Johnson, E.O., Zhang, A., Zhou, W., Rao, Z. and 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 Trans, 41 (28), 8703-14. PDF

 

Abdalla, J.A.B.; Bowen, A.M.; Bell, S.G.; Wong , L.L.; Timmel, C.R.; Harmer, J. (2012) Characterisation of the paramagnetic [2Fe–2S]⁺ centre in palustrisredoxin-B (PuxB) from Rhodopseudomonas palustris CGA009: g-matrix determination and spin coupling analysis, Phys Chem Chem Phys, 14 (18), 6519-30. PDF

 

Bell, S.G., Yang, W., Yorke, J.A., Zhou, W., Wang, H., Harmer, J., Copley, R., Zhang, A., Zhou, R., Bartlam, M., Rao, Z. and Wong, L.-L. (2012) Structure and function of CYP108D1 from Novosphingobium aromaticivorans DSM12444: an aromatic hydrocarbon binding P450 enzyme. Acta Crystallogr Sect D Biol Cryst, 68 (3), 277-291. PDF

 

Whitehouse, C.J.C., Bell, S.G. and Wong, L.-L. (2012) P450BM3 (CYP102A1): Connecting the dots. Chem Soc Rev, 41 (3), 1218-1260. PDF

 

Whitehouse, C.J.C., Yang, W., Yorke, J.A., Tufton H.G., Ogilvie, L.C.I., Bell, S.G., Zhou, W. Bartlam, M., Rao Z. and Wong L.-L. Structural analysis, electronic properties and catalytic behaviour of an activity-enhancing CYP102A1 (P450BM3) variant, Dalton Trans, 40 (40) 10383-10396. PDF

 

Whitehouse, C.J.C., Rees, N.H., Bell, S.G. and Wong L.-L. (2011) Dearomatisation of xylene by P450BM3 (CYP102A1). Chem Eur J, 17, 6862-6868. PDF

 

Ma, M., Bell, S.G., Yang, W., Hao, Y., Rees, N.H., Bartlam, M., Zhou, W., Wong, L.-L. and Rao, Z. (2011) Structural analysis of CYP101C1 from Novosphingobium aromaticivorans DSM12444. ChemBioChem, 12 (1), 88-99.

 

Yang, W., Bell, S.G., Wang, H., Zhou, W., Bartlam, M., Wong, L.-L. and Rao, Z. (2011) The structure of CYP101D2 unveils a potential path for substrate entry into the active site. Biochem J, 433 (1), 85-93.PDF

 

Whitehouse, C.J.C., Yang, W., Yorke, J.A., Rowlett, B.C., Strong, A.J.F., Blanford, C.F., Bell, S.G., Bartlam, M., Rao Z. and Wong L.-L. (2010) Structural basis for the properties of two single-site proline mutants of CYP102A1 (P450BM3) ChemBioChem, 11, 2549-2556.

 

Cryle, M.J., Bell, S.G. and Schlicting, I. (2010) Structural and biochemical characterisation of the cytochrome P450 CypX from Bacillus subtilis: A cyclic Leu-Leu dipeptide oxidase. Biochemistry, 49 (34):7282-7296. PDF

 

Yang, W., Bell, S.G., Wang, H., Zhou, W., Hoskins, N., Dale, A., Bartlam, M., Wong, L.-L. and Rao, Z. (2010) Molecular characterization of a class I P450 electron transfer system from Novosphingobium aromaticivorans DSM12444. J Biol Chem, 285 (35), 27372-27384. PDF

 

Xu, F., Bell, S.G., Peng, Y., Johnson, E. O., Bartlam, M., Rao, Z. and Wong, L.-L. (2009) Crystal structure of a ferredoxin reductase for the CYP199A2 system from Rhodopseudomonas palustris. Proteins, 77 (4), 867-880. PDF

 

Lovett, J. E., Bowen, A. M., Timmel, C. R., Jones, M. W., Dilworth, J. R., Caprotti, D., Bell, S. G., Wong, L.-L. and Harmer, J. (2009) Structural information from orientationally selective DEER spectroscopy. Phys Chem Chem Phys, 11, 6840-6848. PDF

 

Whitehouse, C. J. C., Bell, S. G., Yang, W., Yorke, J. A., Blanford, C. F., Strong, A. J. F, Morse, E. J., Bartlam, M., Rao Z. and Wong L.-L. (2009) A highly active single-mutation variant of P450BM3. (CYP102A1). Chembiochem, 10 (10), 1654-1656. PDF

 

Bell, S. G. and Vallee B. L. (2009) The Metallothionein/Thionein system: an oxidoreductive metabolic zinc link. Chembiochem, 10 (1), 55-62. PDF

 

Whitehouse, C. J. C., Bell, S. G. and Wong, L.-L. (2008) The desaturation of alkylbenzenes by P450BM3. Chem Eur J, 14 (35), 10905-10908. PDF

 

Bell, S. G., Xu, F., Forward I., Bartlam M., Rao Z. and Wong L.-L. (2008) Crystal structure of CYP199A2, a para-substituted benzoic acid oxidizing cytochrome P450 from Rhodopseudomonas palustris. J Mol Biol, 383 (3), 561-574. PDF

 

Whitehouse, C. J. C., Bell, S. G., Tufton, H. G., Kenny, R. J. P., Ogilvie, L. C. I. and Wong, L.-L. (2008) Evolved CYP102A1 (P450BM3) variants oxidise a range of non-natural substrates and offer new selectivity options Chem Comm, 28 (8), 966-968. PDF

 

Bell, S. G. Hoskins, N., Whitehouse, C. J. C. and Wong, L.-L. (2007) Design and Engineering of Cytochrome P450 systems', in A. Sigel, H. Sigel, R.K.O. Sigel (eds.), Metal Ions in Life Sciences, Vol. 3, The Ubiquitous Roles of Cytochrome P450 Proteins, John Wiley & Sons, Chichester, 437-476. Summary PDF

 

Bell S. G. and Wong L.-L. (2007) P450 enzymes from the bacterium Novosphingobium aromaticivorans. Biochem Biophys Res Commun, 360 (3), 666-672. PDF

 

Bell, S. G., Hoskins, N., Xu, F., Caprotti, D., Rao, Z., and Wong, L.-L. (2006) Cytochrome P450 enzymes from the metabolically diverse bacterium Rhodopseudomonas palustris. Biochem Biophys Res Commun, 342 (1), 191-196. PDF

 

Wong, L.-L. and Bell S. G. (2005) Heme Proteins: Mono- and Dioxygenases. Encyclopedia of Inorganic Chemistry. Summary  PDF   

 

Xu, F., Bell, S.G., Lednik, J., Insley, A., Rao, Z. and Wong, L.-L. (2005) The heme monooxygenase cytochrome P450cam can be engineered to oxidize ethane to ethanol. Angew Chem Int Ed, 44 (26), 4029-4032. PDF

 

Bell, S.G., Chen, X., Sowden, R.J., Xu, F., Williams, J.N., Wong, L.-L. and Rao, Z. (2003) Molecular recognition in (+)-alpha-pinene oxidation by cytochrome P450cam. J Am Chem Soc, 125 (3), 705-714. PDF

 

Bell, S.G., Sowden, R.J. and Wong, L.-L. (2001) Engineering the haem monooxygenase cytochrome P450 for monoterpene oxidation. Chem Commun, 635-636. PDF

 

 

 

 

 

Entry last updated: Wednesday, 14 Nov 2012