
Overview
Background
The molecular evolution of cytochrome P450 Enzymes: biological catalysts of unprecedented versatility.
Cytochrome P450 enzymes (CYPs, P450s) especially those responsible for drug metabolism in humans, are the unifying theme of the research in our lab. These fascinating enzymes are catalysts of exceptional versatility, and functional diversity. In humans they are principally responsible for the clearance of a practically unlimited variety of chemicals from the body, but are also critical in many important physiological processes. In other organisms (plants, animals, bacteria, fungi, almost everything!) they carry out an unprecedented range of functions, such as defense, chemical communication, neural development and even pigmentation. P450s are involved in the biosynthesis of an unequalled range of potent, biologically active natural products in microbes, plants and animals, including many antibiotics, plant and animal hormones, signalling molecules, toxins, flavours and fragrances. We are studying how P450s have evolved to deal with novel substrates by reconstructing ancestral precursors and evolutionary pathways, to answer such questions as how did the koala evolve to live on eucalyptus leaves, a toxic diet for most mammals.
The capabilities of P450s are only just coming to be fully recognized and structural studies on P450s should yield critical insights into how enzyme structure determines function. For example, recently we discovered that P450s are present within cells in the Fe(II) form, a finding that has led to a radical revision of the dogma concerning the P450 catalytic cycle, and has implications for the control of uncoupling of P450 activity in cells. Importantly, the biotechnological potential of P450s remains yet to be exploited. All of the specific research themes detailed below take advantage of our recognized expertise in the expression of recombinant human cytochrome P450 enzymes in bacteria. Our group is interested in finding out how P450s work and how they can be made to work better.
Artificial evolution of P450s for drug development and bioremediation: a way of exploring the sequence space and catalytic potential of P450s. The demonstrated catalytic diversity of P450 enzymes makes them the ideal starting material for engineering sophisticated chemical reagents to catalyse difficult chemical transformations. We are using artificial (or directed) evolution to engineer enzymes that are more efficient, robust and specialized than naturally occurring enzymes with the aim of selecting for properties that are commercially useful in the areas of drug discovery and development and bioremediation of pollutants in the environment. The approach we are using also allows us to explore the essential sequence and structural features that underpin all ~12000 known P450s so as to determine how they work.
Synthetic biology of enzymes for clean, green, solar-powered chemistry in drug development, bioremediation and biosensors. We have identified ancestral enzymes that are extremely thermostable compared to their modern counterparts, making them potentially very useful in industry, since they can withstand long incubations at elevated temperatures. They can be used as ‘off the shelf’ reagents to catalyse useful chemistry, such as in in drug discovery and development, fine chemicals synthesis, and cleaning up the environment. Working with drug companies, we are exploring how they can be best deployed in chemical processes and what structural features make them efficient, robust and specialized. We are also immobilizing P450s in virus-like-particles as ‘designer’ reagents that can be recovered from reactions and reused. To make such processes cheaper and more sustainable, we are using photosynthesis to power P450 reactions for clean, green biocatalysis in microalgae.
Biosketch:
After graduating from UQ with first class Honours in Biochemistry, Elizabeth took up a Royal Commission for the Exhibition of 1851 Overseas Scholarship to pursue doctoral work at Oxford University then undertook postdoctoral work at the Center in Molecular Toxicology and Department of Biochemistry at Vanderbilt University School of Medicine with Prof. F.P. Guengerich. She returned to UQ in 1993 to take up a position in Pharmacology and joined the School of Chemistry and Molecular Biosciences in 2009 as a Professor of Biochemistry.
Availability
- Professor Elizabeth Gillam is:
- Available for supervision
- Media expert
Fields of research
Qualifications
- Bachelor (Honours) of Science (Advanced), The University of Queensland
- Doctor of Philosophy, University of Oxford
Research interests
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Protein engineering
Enzymes such as cytochromes P450 are powerful, specific catalysts that could be very useful in making chemical industries more sustainable and environmentally benign. However naturally occurring enzymes usually cannot survive the long process times and elevated temperatures used in industry. We are engineering enzymes to be thermostable, to tolerate organic solvents and to use alternative cofactors so that they can be employed as designer biocatalysts for the pharmaceutical and other chemical industries.
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Synthetic Biology
We are developing novel systems for biocatalysis to replace energy-intensive steps in chemical processes, such as in the synthesis of drugs, with more sustainable alternatives using enzymes. We are engineering cytochrome P450 enzymes as biocatalysts, attaching them to protein cages and linking them to photosynthesis as a green energy source.
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Molecular evolution
Plants and the animals that consume them are locked in an evolutionary battle involving chemical warfare: plants produce toxins to discourage animals from eating them and in turn, animals develop enzymes to metabolise the plant toxins. We are studying the way enzymes in animals have evolved to respond to the changing chemical environment presented by plant secondary metabolism, processes that have a direct bearing on the ability of people to metabolise drugs and other environmental chemicals.
Research impacts
Our research is leading to the development of more sustainable, environmentally friendly, chemical processes to accelerate drug development and improve the safety of medicines. Our studies into the evolution of catalytic promiscuity in P450s reveal how organisms have evolved to deal with chemicals in the environment and provide insights as to how enzymes develop novel functions. More broadly, the methods that we have developed with colleagues at UQ and in industry for the ancestral reconstruction of P450s and their implementation as sophisticated biocatalysts in industry can be applied to the optimisation of other proteins and enzymes for biotechnological application.
Works
Search Professor Elizabeth Gillam’s works on UQ eSpace
2025
Journal Article
Exploring extreme environments in Türkiye for novel P450s through metagenomic analysis
Mumcu, Hande, Zaugg, Julian, Keles, Irem, Kayrav, Aycan, Balci, Nurgul, Nelson, David R., Hugenholtz, Philip, Gillam, Elizabeth M. J. and Gul Karaguler, Nevin (2025). Exploring extreme environments in Türkiye for novel P450s through metagenomic analysis. PLoS One, 20 (9) e0330523, e0330523-9. doi: 10.1371/journal.pone.0330523
2024
Journal Article
Sequence diversity in the monooxygenases involved in oxime production in plant defense and signaling: a conservative revision in the nomenclature of the highly complex CYP79 family
Koleva, Donka Teneva, Bengochea, Anthony W., Mellor, Silas B., Ochoa-Fernandez, Rocio, Nelson, David R., Møller, Birger Lindberg, Gillam, Elizabeth M. J. and Sørensen, Mette (2024). Sequence diversity in the monooxygenases involved in oxime production in plant defense and signaling: a conservative revision in the nomenclature of the highly complex CYP79 family. Plant Journal, 120 (3), 1236-1256. doi: 10.1111/tpj.17044
2024
Journal Article
Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff
Boyle, Gabriel E., Sitko, Katherine A., Galloway, Jared G., Haddox, Hugh K., Bianchi, Aisha Haley, Dixon, Ajeya, Wheelock, Melinda K., Vandi, Allyssa J., Wang, Ziyu R., Thomson, Raine E. S., Garge, Riddhiman K., Rettie, Allan E., Rubin, Alan F., Geck, Renee C., Gillam, Elizabeth M. J., DeWitt, William S., Matsen, Frederick A. and Fowler, Douglas M. (2024). Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff. Genetics, 228 (3) iyae156. doi: 10.1093/genetics/iyae156
2024
Journal Article
Thermostable fatty acid hydroxylases from ancestral reconstruction of cytochrome P450 family 4 enzymes
Harris, Kurt L., Zhang, Yichi, Yang, Jade, Zeigler, Maxwell B., Thomson, Raine E. S., Carrera-Pacheco, Saskya E., Russell, Drake, Okada, Shoko, Strohmaier, Silja J., Gumulya, Yosephine, Scott, Colin, Totah, Rheem A. and Gillam, Elizabeth M. J. (2024). Thermostable fatty acid hydroxylases from ancestral reconstruction of cytochrome P450 family 4 enzymes. Catalysis Science & Technology, 14 (15), 4211-4227. doi: 10.1039/d4cy00090k
2024
Journal Article
Engineering Biocatalysts for the C−H Activation of Fatty Acids by Ancestral Sequence Reconstruction**
Jones, Bethan S., Ross, Connie M., Foley, Gabriel, Pozhydaieva, Nadiia, Sharratt, Joseph W., Kress, Nico, Seibt, Lisa S., Thomson, Raine E. S., Gumulya, Yosephine, Hayes, Martin A., Gillam, Elizabeth M. J. and Flitsch, Sabine L. (2024). Engineering Biocatalysts for the C−H Activation of Fatty Acids by Ancestral Sequence Reconstruction**. Angewandte Chemie, 136 (18). doi: 10.1002/ange.202314869
2024
Journal Article
Biocatalysis using thermostable cytochrome P450 enzymes in bacterial membranes - comparison of metabolic pathways with human liver microsomes and recombinant human enzymes
Jurva, Ulrik, Sandinge, Ann-Sofie, Baek, Jong Min, Avanthay, Mickael, Thomson, Raine E.S., D'Cunha, Stephlina A, Andersson, Shalini, Hayes, Martin A. and Gillam, Elizabeth M. J. (2024). Biocatalysis using thermostable cytochrome P450 enzymes in bacterial membranes - comparison of metabolic pathways with human liver microsomes and recombinant human enzymes. Drug Metabolism and Disposition, 52 (3), 442-251. doi: 10.1124/dmd.123.001569
2024
Journal Article
Engineering Biocatalysts for the C‐H Activation of Fatty Acids by Ancestral Sequence Reconstruction
Jones, Bethan S., Ross, Connie M., Foley, Gabriel, Pozhydaieva, Nadiia, Sharratt, Joseph W., Kress, Nico, Seibt, Lisa S., Thomson, Raine E. S., Gumulya, Yosephine, Hayes, Martin A., Gillam, Elizabeth M. J. and Flitsch, Sabine (2024). Engineering Biocatalysts for the C‐H Activation of Fatty Acids by Ancestral Sequence Reconstruction. Angewandte Chemie International Edition, 63 (18) e202314869, 1-10. doi: 10.1002/anie.202314869
2023
Journal Article
Strigolactones and shoot branching: what is the real hormone and how does it work?
Dun, Elizabeth A., Brewer, Philip B., Gillam, Elizabeth M. J. and Beveridge, Christine A. (2023). Strigolactones and shoot branching: what is the real hormone and how does it work?. Plant And Cell Physiology, 64 (9), 967-983. doi: 10.1093/pcp/pcad088
2023
Journal Article
Solar-powered P450 catalysis: Engineering electron transfer pathways from photosynthesis to P450s
Agustinus, Bernadius and Gillam, Elizabeth M.J. (2023). Solar-powered P450 catalysis: Engineering electron transfer pathways from photosynthesis to P450s. Journal of Inorganic Biochemistry, 245 112242, 1-12. doi: 10.1016/j.jinorgbio.2023.112242
2023
Journal Article
Opportunities for accelerating drug discovery and development by using engineered drug-metabolizing enzymes
Gillam, Elizabeth M. J. and Kramlinger, Valerie M (2023). Opportunities for accelerating drug discovery and development by using engineered drug-metabolizing enzymes. Drug Metabolism and Disposition, 51 (3), 392-402. doi: 10.1124/dmd.121.000743
2023
Journal Article
Exploiting photosynthesis-driven P450 activity to produce indican in tobacco chloroplasts
Mellor, Silas B., Behrendorff, James B. Y. H., Ipsen, Johan Ø., Crocoll, Christoph, Laursen, Tomas, Gillam, Elizabeth M. J. and Pribil, Mathias (2023). Exploiting photosynthesis-driven P450 activity to produce indican in tobacco chloroplasts. Frontiers in Plant Science, 13 1049177, 1-17. doi: 10.3389/fpls.2022.1049177
2022
Journal Article
Engineering indel and substitution variants of diverse and ancient enzymes using Graphical Representation of Ancestral Sequence Predictions (GRASP)
Foley, Gabriel, Mora, Ariane, Ross, Connie M., Bottoms, Scott, Sützl, Leander, Lamprecht, Marnie L., Zaugg, Julian, Essebier, Alexandra, Balderson, Brad, Newell, Rhys, Thomson, Raine E. S., Kobe, Bostjan, Barnard, Ross T., Guddat, Luke, Schenk, Gerhard, Carsten, Jörg, Gumulya, Yosephine, Rost, Burkhard, Haltrich, Dietmar, Sieber, Volker, Gillam, Elizabeth M. J. and Bodén, Mikael (2022). Engineering indel and substitution variants of diverse and ancient enzymes using Graphical Representation of Ancestral Sequence Predictions (GRASP). PL o S Computational Biology, 18 (10) e1010633, e1010633. doi: 10.1371/journal.pcbi.1010633
2022
Journal Article
Engineering functional thermostable proteins using ancestral sequence reconstruction
Thomson, Raine E.S., Carrera-Pacheco, Saskya E. and Gillam, Elizabeth M.J. (2022). Engineering functional thermostable proteins using ancestral sequence reconstruction. Journal of Biological Chemistry, 298 (10) 102435, 1-16. doi: 10.1016/j.jbc.2022.102435
2022
Journal Article
Ancestral sequence reconstruction of the CYP711 family reveals functional divergence in strigolactone biosynthetic enzymes associated with gene duplication events in monocot grasses
Vinde, Marcos H., Cao, Da, Chesterfield, Rebecca J., Yoneyama, Kaori, Gumulya, Yosephine, Thomson, Raine E. S., Matila, Tebogo, Ebert, Birgitta E., Beveridge, Christine A., Vickers, Claudia E. and Gillam, Elizabeth M. J. (2022). Ancestral sequence reconstruction of the CYP711 family reveals functional divergence in strigolactone biosynthetic enzymes associated with gene duplication events in monocot grasses. New Phytologist, 235 (5), 1900-1912. doi: 10.1111/nph.18285
2022
Journal Article
Ancestral sequence reconstruction of a cytochrome P450 family involved in chemical defense reveals the functional evolution of a promiscuous, xenobiotic-metabolizing enzyme in vertebrates
Harris, Kurt L., Thomson, Raine E.S., Gumulya, Yosephine, Foley, Gabriel, Carrera-Pacheco, Saskya E., Syed, Parnayan, Janosik, Tomasz, Sandinge, Ann-Sofie, Andersson, Shalini, Jurva, Ulrik, Bodén, Mikael and Gillam, Elizabeth M.J. (2022). Ancestral sequence reconstruction of a cytochrome P450 family involved in chemical defense reveals the functional evolution of a promiscuous, xenobiotic-metabolizing enzyme in vertebrates. Molecular Biology and Evolution, 39 (6) msac116. doi: 10.1093/molbev/msac116
2022
Book Chapter
Using the evolutionary history of proteins to engineer insertion-deletion mutants from robust, ancestral templates using Graphical Representation of Ancestral Sequence Predictions (GRASP)
Ross, Connie M., Foley, Gabriel, Boden, Mikael and Gillam, Elizabeth M. J. (2022). Using the evolutionary history of proteins to engineer insertion-deletion mutants from robust, ancestral templates using Graphical Representation of Ancestral Sequence Predictions (GRASP). Enzyme engineering. (pp. 85-110) edited by Francesca Magnani, Chiara Marabelli and Francesca Paradisi. New York, NY, United States: Humana Press. doi: 10.1007/978-1-0716-1826-4_6
2022
Book Chapter
Use of engineered cytochromes P450 for accelerating drug discovery and development
Thomson, Raine E.S., D'Cunha, Stephlina A., Hayes, Martin A. and Gillam, Elizabeth M.J. (2022). Use of engineered cytochromes P450 for accelerating drug discovery and development. Pharmacology and toxicology of cytochrome P450 – 60th anniversary. (pp. 195-252) edited by Hiroshi Yamazaki. Cambridge, MA, United States: Academic Press. doi: 10.1016/bs.apha.2022.06.001
2021
Journal Article
Resurrection and characterization of ancestral CYP11A1 enzymes
Hartz, Philip, Strohmaier, Silja J., EL‐Gayar, Basma M., Abdulmughni, Ammar, Hutter, Michael C., Hannemann, Frank, Gillam, Elizabeth M. J. and Bernhardt, Rita (2021). Resurrection and characterization of ancestral CYP11A1 enzymes. The FEBS Journal, 288 (22) febs.16054, 6510-6527. doi: 10.1111/febs.16054
2020
Book Chapter
Directed evolution of enzymes
Jackson, Colin J., Gillam, Elizabeth M.J. and Ollis, David L. (2020). Directed evolution of enzymes. Comprehensive Natural Products III: Chemistry and biology. (pp. 654-673) London, United Kingdom: Elsevier. doi: 10.1016/B978-008045382-8.00675-4
2020
Journal Article
Oxygen surrogate systems for supporting human drug-metabolizing cytochrome P450 enzymes
Strohmaier, Silja J., De Voss, James J., Jurva, Ulrik, Andersson, Shalini and Gillam, Elizabeth M. J. (2020). Oxygen surrogate systems for supporting human drug-metabolizing cytochrome P450 enzymes. Drug Metabolism and Disposition , 48 (6), 432-437. doi: 10.1124/dmd.120.090555
Funding
Current funding
Supervision
Availability
- Professor Elizabeth Gillam is:
- Available for supervision
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Supervision history
Current supervision
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Doctor Philosophy
Engineering cytochrome P450 family 4 enzymes for biocatalysis using ancestral sequence reconstruction
Principal Advisor
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Doctor Philosophy
Nano-scale bioreactors: virus-like particles used as reusable scaffolds for designer cytochrome P450 enzymes
Principal Advisor
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Doctor Philosophy
Development of Cytochrome P450 Enzymes as Biocatalysts for Metabolite and Novel Drug Candidate Synthesis for the Pharmaceutical Industry.
Principal Advisor
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Doctor Philosophy
Evolution of cytochrome P450 enzymes in response to dietary and environmental chemicals
Principal Advisor
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Doctor Philosophy
Insect P450s for degradation of polyethylene plastic
Principal Advisor
Other advisors: Associate Professor Paul Ebert
Completed supervision
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2024
Doctor Philosophy
Coupling of P450 ancestors with the photosynthetic machinery of Chlamydomonas reinhardtii for light-driven biocatalysis in vitro
Principal Advisor
Other advisors: Dr Ian Ross, Professor Ben Hankamer
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2022
Doctor Philosophy
Ancestral reconstruction and characterisation of the CYP2U subfamily
Principal Advisor
Other advisors: Professor Mikael Boden
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2021
Doctor Philosophy
Engineering stable cytochrome P450 2D forms as competent biocatalysts for industrial applications
Principal Advisor
Other advisors: Professor Luke Guddat
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2021
Doctor Philosophy
Structural and functional characterisation of ancestral cytochromes P450 from family 2 in tetrapods
Principal Advisor
Other advisors: Professor Luke Guddat
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2020
Doctor Philosophy
Development and Characterisation of Cytochrome P450 Support Systems
Principal Advisor
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2020
Doctor Philosophy
Ancestral reconstruction of cytochrome P450 family 1, 4 and cytochrome P450 reductase: Insights into evolution and applications in biocatalysis
Principal Advisor
Other advisors: Professor Mikael Boden
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2013
Doctor Philosophy
Characterisation of the expression of indole-metabolising cytochrome P450 enzymes in the human brain
Principal Advisor
Other advisors: Dr Simon Worrall
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2012
Doctor Philosophy
Directed evolution of enzymes of cytochrome P450 catalysis: Evolving CYP1A, CYP2D and P450 reductase
Principal Advisor
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2011
Doctor Philosophy
Investigations of cytochromes P450 using the DNA family shuffling method.
Principal Advisor
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2007
Doctor Philosophy
REDOX PROPERTIES AND MEMBRANE LOCALIZATION OF HUMAN RECOMBINANT CYTOCHROME P450 SYSTEMS
Principal Advisor
Other advisors: Professor Paul Bernhardt
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2005
Doctor Philosophy
MOLECULAR BREEDING OF CYTOCHROME P450s FOR INDIGOID PIGMENT PRODUCTION
Principal Advisor
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2004
Doctor Philosophy
THE INITIATION OF AUTO-IMMUNE REACTIONS ON ANTI-CONVULSANT INDUCED HYPERSENSITIVITY: THE ROLE OF CYTOCHROME P450 ENZYMES
Principal Advisor
Other advisors: Dr Simon Worrall
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2023
Doctor Philosophy
Novel terpene based agrochemicals: Exploring cytochromes P450 mediated diversification of the strigolactone structure
Associate Advisor
Other advisors: Dr Birgitta Ebert
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2022
Doctor Philosophy
Methods for ancestral sequence reconstruction of large and complex protein families
Associate Advisor
Other advisors: Emeritus Professor Ross Barnard, Associate Professor Michael Landsberg, Professor Mikael Boden
Media
Enquiries
Contact Professor Elizabeth Gillam directly for media enquiries about:
- Bacterial expression
- Biocatalysis
- Bioremediation
- Chemical industries
- Drug discovery
- Drug metabolism
- Enzymes
- Human cytochrome P450 enzymes
- Molecular toxicology
- P450 enzymes
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