Research Interests
Biocatalysis and Enzyme Technology Biochemistry & Molecular Biology Bioinorganic Chemistry Bioprocessing, Bioproduction and Bioproducts Bioremediation Biotechnology Catalysis and Mechanisms of Reactions Chemical Sciences Enzymes Industrial Microbiology Industrial Molecular Engineering of Nucleic Acids and Proteins Inorganic Chemistry Medical Biochemistry: Proteins and Peptides Organic Chemical Synthesis Organic Chemistry Proteins and Peptides Structural Chemistry and Spectroscopy Synthetic BiologyAPrf Stephen Bell
Associate Professor
School of Physics, Chemistry and Earth Sciences
College of Sciences
Eligible to supervise Masters and PhD - email supervisor to discuss availability.
Enzyme CatalysisStudents are working on wide range of projects related to the application of enzyme for chemical synthesis using interdisciplinary methods from Biochemistry, Synthetic Biology and Chemistry suitable for students with a background in Chemistry and Biological Science with an interest in enzyme biocatalysis, chemical synthesis, the structure of metalloproteins, microbiology of secondary metabolite synthesis and how proteins/enzymes have evolved to function.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 and archaea which are capable of binding and oxidising a wide range of organic compounds. We currently focus on steroid and terpenoid oxidising enzymes from a range of microorganisms. Many of these microbes have evolved to survive in extreme conditions (e.g. temperature and pH) and we are exploring these robust enzymes as biocatalysts using new methods developed by graduate students here at Adelaide.We also 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 to1) to study the mechanism of action of these enzymes which is important in understanding drug metabolism and design2) Determine the structure of the enzymes by X-ray crystallography and other techniques such as NMR and Mass Spectroscopy3) Immobilise the enzymes on different solid state supports to enhance their stability and lifetime.
The isolation and study of cytochrome P450 enzymes for biocatalysis and medicinal chemistry
The cytochrome P450 superfamily of haem iron monooxygenases is found in virtually all living organisms. They are important biocatalysts that can selectively oxidise 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 oxidation reactions holds great promise for biotechnological applications as these reactions are challenging to perform using traditional chemical synthesis. In the lab we study these cytochrome P450 enzymes for biocatalysis and organic synthesis applications. The ultimate goal is to develop these systems as robust biocatalysts for clean, sustainable, low energy oxidation processes in natural product synthesis (e.g. flavour and fragrance compounds) and bioremediation of recalcitrant compounds (e.g. polyaromatic hydrocarbons, resin acids and lignin mononmers).
We identify new enzymes from a wide range of bacteria and archaea and assess their function and potential applications. Projects include
1) designing and testing inhibitors for P450 enzymes from pathogenic bacteria such as Mycobacterium tuberculosis
2) assessing the role of P450 enzymes from bacteria in secondary metabolism (steroids, terpenoid and natural product oxidation) to generate high-value chemicals or to break down toxic compounds (bioremediation of aromatics and toxins)
3) the development of efficient and thermostable oxygenase bicatalysts from extremophile organisms
We alter the sequence of these cytochrome P450 enzymes to change their function. We 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 P450 enzymes that are capable of selectively hydroxylating terpenoids and steroids. We have recently identified P450 enzymes which can tolerate conditions not usually suited for enzyme chemistry (high temperature, organic solvent and pH extremes). Using a method developed in Adelaide we modify these enzymes so they can efficiently use hydrogen peroxide to catalyse their reactions. Together this simplifies their application.
We have an interest in their electron transfer partners (e.g. iron-sulphur ferredoxin proteins and flavoproteins) in order to improve the efficiency of the purified enzymes and which is essential to design efficient whole-cell oxidation systems using synthetic biology. We have developed 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 which was set up to use biocatalysis to generate high -value compounds. This was successfully achieved on a tonne scale which to generate products used in the flavour and fragrance industry.
Students undertake a wide range of activities at the interface of Chemistry, Biochemistry, Synthetic Biology including protein synthesis and enzyme assays (biochemistry), and protein engineering (molecular biology). Scale-up of the enzyme activity and inhibitor synthesis requires organic chemistry techniques (synthesis) and analytical chemistry (HPLC, GC-MS etc.). This provides an excellent platform for students seeking jobs outside of academia. We also explore the structure of these enzymes using X-ray crystallography (variable temperature studies). Members of the group have also undertakem other spectroscopic techniques including, electrochemistry and EPR (electron paramagnetic resonance) studies of these cytochrome P450 enzymes at Adelaide and in collaboration with others.
The Australian Research Council has funded our research into P450 mechanism and the design of enzyme inhibitors through Discovery Project Grants. My research into isolating and understanding novel P450 electron transfer partners has been funded through an ARC Future Fellowship. Currently our research into designing new thermostable enzymes for a series of reactions is funded by an ARC Discovery project.
My group currently consists of 7-8 PhD Students and I have extensive experience in supervising Honours students.
Potential research students are directed to the Adelaide Graduate Centre for information on admissions, applications and scholarship
https://www.adelaide.edu.au/graduate-research/
Questions regarding typical research projects can be directed to Dr Bell.
| Date | Position | Institution name |
|---|---|---|
| 2017 - 2019 | Associate Professor and ARC Future Fellow | University of Adelaide |
| 2017 - ongoing | Associate Professor | University of Adelaide |
| 2015 - 2016 | Senior Lecturer and ARC Future Fellow | University of Adelaide |
| 2012 - 2014 | Lecturer | University of Adelaide |
| Date | Type | Title | Institution Name | Country | Amount |
|---|---|---|---|---|---|
| 2016 | Teaching Award | OLT Citation for Outstanding Contributions to Student Learning | University of Adelaide/Australian Government Department of Education and Training | Australia | - |
| 2015 | Fellowship | ARC Future Fellowship | University of Adelaide | Australia | - |
| 2013 | Achievement | Founding Shareholder of Oxford Biotrans | - | United Kingdom | - |
| Date | Institution name | Country | Title |
|---|---|---|---|
| Oxford university | United Kingdom | DPhil | |
| University of Oxford | United Kingdom | BA and MA Chemistry (Oxon) |
| Year | Citation |
|---|---|
| 2017 | Harbort, J. S., De Voss, J. J., Stok, J. E., Bell, S. G., & Harmer, J. R. (2017). CW and Pulse EPR of Cytochrome P450 to Determine Structure and Function. In L. Berliner, & G. Hanson (Eds.), Future Directions in Metalloprotein and Metalloenzyme Research (Vol. 13, pp. 103-142). Switzerland: Springer. DOI |
| 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. DOI Scopus15 |
| 2007 | Bell, S., Hoskins, N., Whitehouse, C., & Wong, L. (2007). Design and engineering of cytochrome P450 systems. In A. Sigel, H. Sigel, & R. 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 Scopus28 |
| 2005 | Wong, L., & Bell, S. G. (2005). Iron: Heme Proteins, Mono‐ & DioxygenasesBased in part on the article Iron: Heme Proteins, Mono‐ & Dioxygenases by Masanori Sono & John H. Dawson which appeared in the <i>Encyclopedia of Inorganic Chemistry, First Edition</i> .. Wiley. DOI |
| Year | Citation |
|---|---|
| 2017 | Wong, S. H., Bell, S. G., & De Voss, J. J. (2017). P450 catalysed dehydrogenation. In Proceedings of the 23rd International Conference on Physical Organic Chemistry (ICPOC-23 2016) as published in Pure and Applied Chemistry Vol. 89 (pp. 841-852). Germany: Walter de Gruyter. DOI Scopus20 WoS19 |
| 2010 | Wong, L. L., Whitehouse, C. J. C., Yang, W., Yorke, J. A., Blanford, C. F., Bell, S. G., . . . Rao, Z. (2010). Engineering P450s by Rational Design. In DRUG METABOLISM REVIEWS Vol. 42 (pp. 20). Istanbul, TURKEY: INFORMA HEALTHCARE. |
| Year | Citation |
|---|---|
| 2015 | Williamson, N. M., Huang, D. M., Bell, S. G., & Metha, G. F. (2015). Guided Inquiry Learning in an Introductory Chemistry Course. Poster session presented at the meeting of International Chemical Congress of Pacific Basin Societies (Pacifichem). Honolulu, USA. |
| 2012 | Williamson, N. M., Metha, G. F., Huang, D. M., & Bell, S. G. (2012). Development of POGIL-Style Organic Chemistry Activities. Poster session presented at the meeting of Proceedings of the Australian Conference on Science and Mathematics Education. Sydney. |
| Year | Citation |
|---|---|
| 2009 | Wong, L., Bell, S., & Whitehouse, C. (2009). Mutant Enzymes. Great Britan. |
| Year | Citation |
|---|---|
| 2024 | Harlington, A., Das, T., Shearwin, K., Bell, S., & Whelan, F. (2024). The S-lignin<i>O</i>-demethylase SyoA: Structural insights into a new class of heme peroxygenase enzymes. DOI |
| 2023 | Akter, J., Hayball, E., & Bell, S. (2023). Efficient regio- and stereo-selective C-H bond hydroxylation of steroids using an engineered heme-thiolate peroxygenase biocatalyst. DOI |
| 2023 | Lee, J., Bruning, J., & Bell, S. (2023). In Crystallo Reactions with an Engineered Cytochrome P450 Peroxygenase. DOI |
Grants and Funding
The Australian Research Council have funded our research into P450 mechanism through Discovery Project Grants and a Future Fellowship
We have grants
1) the role of cholesterol metabolism in Mycobacterium tuberculosis in an effort to inhibit this pathogenic bacterium which cause tuberculosis.
2) the isolation of new thermostable biocatalyst and methods to apply these (immoblisation) for synthetic applications.
3) the design of inhibitors for steroid oxidising P450 enzymes in humans which play a role in prostate cancer.
Teaching
I have taught a broad range of courses across all Levels of Chemistry with a focus on Inorganic Chemistry.
Chem III Inorganic Reaction Mechanisms and Organometallic Chemistry - 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.
I also teach a range of first year courses - Transition metal chemistry, Kinetics and Electrochemistry.
| Date | Role | Research Topic | Program | Degree Type | Student Load | Student Name |
|---|---|---|---|---|---|---|
| 2025 | Co-Supervisor | Discovery and directed evolution of bacterial biosensors | Master of Philosophy | Master | Full Time | Ms Madeline Rose Fechner |
| 2025 | Principal Supervisor | Exploring Cold-Adapted Cytochrome P450 Enzymes from Psychrophilic Organisms: Production, Characterization, and Biotechnological Applications. | Doctor of Philosophy | Doctorate | Full Time | Miss Rabia Mehmood |
| 2025 | Principal Supervisor | Analysis of P450 cytochrome monooxygenases from cyanobacteria | Doctor of Philosophy | Doctorate | Full Time | Ms Samaneh Jafari Porzani |
| 2025 | Principal Supervisor | Study of steroid metabolizing enzymes from actinobacteria and the genus Bacillus | Doctor of Philosophy | Doctorate | Full Time | Ms Sabiha Enam Spriha |
| 2025 | Principal Supervisor | Exploring Cold-Adapted Cytochrome P450 Enzymes from Psychrophilic Organisms: Production, Characterization, and Biotechnological Applications. | Doctor of Philosophy | Doctorate | Full Time | Miss Rabia Mehmood |
| 2025 | Principal Supervisor | Study of steroid metabolizing enzymes from actinobacteria and the genus Bacillus | Doctor of Philosophy | Doctorate | Full Time | Ms Sabiha Enam Spriha |
| 2025 | Principal Supervisor | Analysis of P450 cytochrome monooxygenases from cyanobacteria | Doctor of Philosophy | Doctorate | Full Time | Ms Samaneh Jafari Porzani |
| 2025 | Co-Supervisor | Discovery and directed evolution of bacterial biosensors | Master of Philosophy | Master | Full Time | Ms Madeline Rose Fechner |
| 2024 | Principal Supervisor | Characterization of peroxygenase activity in CYP154 enzymes from the thermophilic bacterium Thermobifida fusca | Doctor of Philosophy | Doctorate | Full Time | Ms Oghenesivwe Osiebe |
| 2024 | Principal Supervisor | Exploration and Exploitation of Novel Thermally Adapted Cytochromes P450 and their Biotechnological Uses | Doctor of Philosophy | Doctorate | Full Time | Mr Delroy Sheng Yu Huang |
| 2024 | Principal Supervisor | The Study of Cholesterol Oxidizing Enzymes from Actinobacteria | Doctor of Philosophy | Doctorate | Full Time | Dr Gashaw Getaneh Dagnaw |
| 2024 | Principal Supervisor | Developing new methods for drug release targeting cell surface receptor density. | Doctor of Philosophy | Doctorate | Full Time | Ms Maya Liza Doyle |
| 2024 | Principal Supervisor | Characterization of peroxygenase activity in CYP154 enzymes from the thermophilic bacterium Thermobifida fusca | Doctor of Philosophy | Doctorate | Full Time | Ms Oghenesivwe Osiebe |
| 2024 | Principal Supervisor | Exploration and Exploitation of Novel Thermally Adapted Cytochromes P450 and their Biotechnological Uses | Doctor of Philosophy | Doctorate | Full Time | Mr Delroy Sheng Yu Huang |
| 2024 | Principal Supervisor | Developing new methods for drug release targeting cell surface receptor density. | Doctor of Philosophy | Doctorate | Full Time | Ms Maya Liza Doyle |
| 2024 | Principal Supervisor | The Study of Cholesterol Oxidizing Enzymes from Actinobacteria | Doctor of Philosophy | Doctorate | Full Time | Dr Gashaw Getaneh Dagnaw |
| 2023 | Principal Supervisor | Engineering CYP17A1 inhibitors for castrate-resistant prostate cancer | Doctor of Philosophy | Doctorate | Full Time | Mr Nikita Yevstigneyev |
| 2023 | Principal Supervisor | Characterization and Structural Study of Cytochrome P450 enzymes from thermophilic bacteria | Doctor of Philosophy | Doctorate | Full Time | Mr Tuhin Das |
| 2023 | Co-Supervisor | Naphtalimide Scaffolds for Optical+XRF multimodal Probes | Doctor of Philosophy | Doctorate | Full Time | Mr Terry Koh |
| 2023 | Co-Supervisor | Naphtalimide Scaffolds for Optical+XRF multimodal Probes | Doctor of Philosophy | Doctorate | Full Time | Mr Terry Koh |
| 2023 | Principal Supervisor | Engineering CYP17A1 inhibitors for castrate-resistant prostate cancer | Doctor of Philosophy | Doctorate | Full Time | Mr Nikita Yevstigneyev |
| 2023 | Principal Supervisor | Characterization and Structural Study of Cytochrome P450 enzymes from thermophilic bacteria | Doctor of Philosophy | Doctorate | Full Time | Mr Tuhin Das |
| 2022 | Principal Supervisor | Combining machine-learning and rational design for engineering heme enzyme biocatalysts and biosensors. | Doctor of Philosophy | Doctorate | Full Time | Miss Alecia Rachel Gee |
| 2022 | Principal Supervisor | Synthesis of inhibitors for steroid metabolising enzymes | Doctor of Philosophy | Doctorate | Full Time | Miss Eva Hayball |
| 2022 | Principal Supervisor | Synthesis of inhibitors for steroid metabolising enzymes | Doctor of Philosophy | Doctorate | Full Time | Miss Eva Hayball |
| 2022 | Principal Supervisor | Combining machine-learning and rational design for engineering heme enzyme biocatalysts and biosensors. | Doctor of Philosophy | Doctorate | Full Time | Miss Alecia Rachel Gee |
| Date | Role | Research Topic | Program | Degree Type | Student Load | Student Name |
|---|---|---|---|---|---|---|
| 2023 - 2024 | Co-Supervisor | Taking the Brakes Off Photocatalytic Drug Uncaging | Master of Philosophy | Master | Full Time | Mr Liam Matthew Carson |
| 2020 - 2024 | Principal Supervisor | Evolution and inhibition of cholesterol catabolising P450 enzymes in pathogenic mycobacteria | Doctor of Philosophy | Doctorate | Full Time | Mr Daniel Zocchi Doherty |
| 2020 - 2024 | Principal Supervisor | The Application of Peroxygenase P450 Enzymes as Selective Oxidation Catalysts | Doctor of Philosophy | Doctorate | Full Time | Ms Jinia Akter |
| 2020 - 2025 | Principal Supervisor | Using CYP199A4 as a Model System to Investigate the Conversion of Cytochrome P450s Into Efficient Peroxygenases | Doctor of Philosophy | Doctorate | Full Time | Mr Matthew Podgorski |
| 2019 - 2023 | Principal Supervisor | Protein and Reaction Engineering of P450 Enzymes for Selective Oxidations | Doctor of Philosophy | Doctorate | Full Time | Dr Joel Hoong Zhang Lee |
| 2019 - 2023 | Principal Supervisor | Understanding cytochrome P450 cholesterol metabolism in bacteria | Doctor of Philosophy | Doctorate | Full Time | Dr Amna Ghith |
| 2018 - 2023 | Principal Supervisor | Structural and Functional Investigations of Cytochrome P450 Enzymes from Mycobacterium Species | Doctor of Philosophy | Doctorate | Full Time | Miss Hebatalla Ahmed Ibrahim Mohamed |
| 2018 - 2020 | Principal Supervisor | Exploring the Monooxygenase Activity and Selectivity of Two Related Cytochrome P450 Enzymes | Master of Philosophy | Master | Full Time | Mr Saurabh Kumar Ahirwar |
| 2017 - 2020 | Principal Supervisor | Investigation of the Mechanism of Multiple Cytochrome P450-catalysed Reactions | Master of Philosophy | Master | Full Time | Mr Matthew Podgorski |
| 2016 - 2018 | Principal Supervisor | Harnessing P450 Enzymes as Biocatalysts for Selective C-H Bond Hydroxylation | Master of Philosophy | Master | Full Time | Dr Joel Hoong Zhang Lee |
| 2016 - 2020 | Principal Supervisor | Enzyme Immobilisation using Porous Frameworks | Doctor of Philosophy | Doctorate | Full Time | Dr Natasha Kate Maddigan |
| 2015 - 2017 | Co-Supervisor | Isolation of New P450s and the Modification of Existing P450s for Biocatalysis | Master of Philosophy | Master | Full Time | Mr Ian Cheuk-Kei Lau |
| 2015 - 2019 | Principal Supervisor | Application of the Monooxygenase Enzymes CYP101B1 and CYP101C1 from Novosphingobium aromaticivorans for Selective and Efficient Functionalisation of Inert C-H Bonds | Doctor of Philosophy | Doctorate | Full Time | Mr Md Raihan Sarkar |
| 2015 - 2019 | Principal Supervisor | Strategies to improve the efficiency of oxidation reactions of the enzyme Cytochrome P450Bm3 | Doctor of Philosophy | Doctorate | Full Time | Ms Shaghayegh Dezvarei |
| 2014 - 2016 | Co-Supervisor | Utilising CYP199A4 from Rhodopseudomonas Palustris HaA2 for Biocatalysis and Mechanistic Studies | Master of Philosophy | Master | Full Time | Miss Rebecca Chao |
| 2014 - 2018 | Principal Supervisor | Utilising CYP199A4 from Rhodopseudomonas palustris HaA2 for investigation of the mechanism of cytochrome P450-catalysed oxidations | Doctor of Philosophy | Doctorate | Full Time | Tom Coleman |
| 2014 - 2018 | Principal Supervisor | Deciphering Electron Transfer and Cytochrome P450 Activity in Mycobacterium marinum | Doctor of Philosophy | Doctorate | Full Time | Ms Stella Agnes Child |
| 2014 - 2016 | Co-Supervisor | Investigations and Applications of Self-Sufficient Cytochrome P450 Monooxygenases | Master of Philosophy | Master | Full Time | Mr Samuel David Munday |
| 2013 - 2015 | Co-Supervisor | The Efficient and Selective Catalytic Oxidation of Terpenoids and Aromatic Hydrocarbons by the P450 Monooxygenase CYP101B1 | Master of Philosophy | Master | Full Time | Emma Ashleigh Hall |