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Professor Elizabeth Gillam
Professor

Elizabeth Gillam

Email: 
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+61 7 336 51410

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

Research interests

  • 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.

  • 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.

  • 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

175 works between 1986 and 2024

1 - 20 of 175 works

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

Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff

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

Engineering Biocatalysts for the C−H Activation of Fatty Acids by Ancestral Sequence Reconstruction**

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

Biocatalysis using thermostable cytochrome P450 enzymes in bacterial membranes - comparison of metabolic pathways with human liver microsomes and recombinant human enzymes

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

Engineering Biocatalysts for the C‐H Activation of Fatty Acids by Ancestral Sequence Reconstruction

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

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

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

Thermostable fatty acid hydroxylases from ancestral reconstruction of cytochrome P450 family 4 enzymes

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

Strigolactones and shoot branching: what is the real hormone and how does it work?

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

Solar-powered P450 catalysis: Engineering electron transfer pathways from photosynthesis to P450s

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

Opportunities for accelerating drug discovery and development by using engineered drug-metabolizing enzymes

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

Exploiting photosynthesis-driven P450 activity to produce indican in tobacco chloroplasts

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

Engineering indel and substitution variants of diverse and ancient enzymes using Graphical Representation of Ancestral Sequence Predictions (GRASP)

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

Engineering functional thermostable proteins using ancestral sequence reconstruction

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

Ancestral sequence reconstruction of the CYP711 family reveals functional divergence in strigolactone biosynthetic enzymes associated with gene duplication events in monocot grasses

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

Ancestral sequence reconstruction of a cytochrome P450 family involved in chemical defense reveals the functional evolution of a promiscuous, xenobiotic-metabolizing enzyme in vertebrates

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

Using the evolutionary history of proteins to engineer insertion-deletion mutants from robust, ancestral templates using Graphical Representation of Ancestral Sequence Predictions (GRASP)

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

Use of engineered cytochromes P450 for accelerating drug discovery and development

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

Resurrection and characterization of ancestral CYP11A1 enzymes

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

Directed evolution of enzymes

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

Oxygen surrogate systems for supporting human drug-metabolizing cytochrome P450 enzymes

2020

Journal Article

Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability

Bart, Aaron G., Harris, Kurt L., Gillam, Elizabeth M. J. and Scott, Emily E. (2020). Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability. Journal of Biological Chemistry, 295 (17), 5640-5653. doi: 10.1074/jbc.ra119.010727

Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability

Funding

Current funding

  • 2023 - 2025
    Moon's Mission: creating a replicable therapeutic framework for hereditary spastic paraplegias.
    NHMRC MRFF Stem Cells Therapies Mission
    Open grant
  • 2020 - 2024
    Nano-reactors: Protein cages as reusable scaffolds for designer enzymes
    ARC Discovery Projects
    Open grant

Past funding

  • 2019 - 2022
    Light driven P450: Using Photosynthesis to Power Fine Chemical Production
    ARC Linkage Projects
    Open grant
  • 2019
    A versatile accurate mass, high resolution QTOF mass spectrometer for chemistry and proteomic applications
    UQ Major Equipment and Infrastructure
    Open grant
  • 2018 - 2019
    Off-the-shelf biocatalysts for fine chemical and pharmaceutical synthesis
    Global Connections Fund
    Open grant
  • 2016 - 2019
    Reconstructing proteins to explain and engineer biological diversity
    ARC Discovery Projects
    Open grant
  • 2015 - 2019
    Thermostable cytochrome P450 enzymes
    UniQuest Pty Ltd
    Open grant
  • 2015
    A sensitive, high resolution QTOF mass spectrometer with nanoUPLC system for qualitative and quantitative biomolecule analysis.
    UQ Major Equipment and Infrastructure
    Open grant
  • 2012 - 2015
    Tracing nature's template: Using statistical machine learning to evolve biocatalysts
    ARC Discovery Projects
    Open grant
  • 2012 - 2013
    Multi angle light scattering detector for the measurement of absolute molecular weight, size, and conformation of macromolecules in solution
    UQ Major Equipment and Infrastructure
    Open grant
  • 2010
    An integrated high -throughput fluorescence imaging facility
    UQ Major Equipment and Infrastructure
    Open grant
  • 2009 - 2010
    Cytochrome P450 libraries for Lead Optimisation in Drug Discovery
    UQ FirstLink Scheme
    Open grant
  • 2007 - 2009
    Evolving enzymes to harness the clean energy reserves of nature
    ARC Discovery Projects
    Open grant
  • 2006
    NHMRC_Infrastructure Item_750w Ultrasonic Processor (SONICATOR) with standard probe, stepped microprobe, glass cup horn, four-element and 96-element probes and noise-abating chamber
    Open grant
  • 2005 - 2008
    Biocatalysts mined from cytochrome P450 Libraries: an innovative tool for accelerating drug development
    ARC Linkage Projects
    Open grant
  • 2004 - 2005
    Molecular Breeding Of Biocatalysts Mined From Cytochrome P450 Libraries: An Innovative Tool for Accelerating Drug Development
    UQ FirstLink Scheme
    Open grant
  • 2002 - 2004
    A novel physiological role for cytochrome P450 enzymes in the brain
    NHMRC Project Grant
    Open grant
  • 2002 - 2004
    Molecular breeding of cytochrome P450 enzymes
    ARC Discovery Projects
    Open grant
  • 1999
    Determinants of substrate binding in sytochrome P450 2C9
    ARC Australian Research Council (Small grants)
    Open grant
  • 1999 - 2001
    Does the active site of cytochrome P450 3A4 accommodate activators and substrates simultaneously?
    ARC Australian Research Council (Large grants)
    Open grant
  • 1998
    HPLC analysis of drug metabolism by recombinant cytochrome P450 enzymes
    Ramaciotti Foundation
    Open grant
  • 1996 - 1998
    Bioactivation of tamoxifen: its role in tamoxifen-induced tumours, covalent binding to protein and in the acquisition of resistance to tamoxifen by tumours
    Kathleen Cuningham Foundation
    Open grant
  • 1996 - 1997
    Bioactivation of tamoxifen: its role in Tamoxifen-induced tumours, covalent binding to protein, and in the acquisition of resistance to tamoxifen by tumours (top up)
    Queensland Cancer Fund
    Open grant
  • 1995 - 1997
    Mechanisms and consequences of covalent binding of phenytoin to tissue proteins
    NHMRC Project Grant - Standard
    Open grant

Supervision

Availability

Professor Elizabeth Gillam is:
Available for supervision

Before you email them, read our advice on how to contact a supervisor.

Available projects

  • Engineering enzymes for bioremediation of microplastics

    Plastics such as polyethylene (PE) are major pollutants in both terrestrial and aquatic environments because they are not easily degraded in nature. Physico-chemical methods for PE remediation are energy intensive and not economically sustainable, raising the possibility of bioremediation instead. The larvae of the greater wax moth (GWM, Galleria mellonella) feed on beeswax, which is rich in long-chain alkanes, and have recently been shown to consume chemically similar low-density PE at considerably higher rates than those currently reported for PE-degrading microbes. Recent work suggests that P450 enzymes may be involved but the mechanism by which this occurs is not yet clear and there is no consensus on how the degradation is achieved biochemically, or even whether it is carried out entirely by the caterpillars themselves or with a contribution from the gut microbiota. Intriguingly, PE breakdown appears to involve a shift to high pH in the lumen of the insect gut, suggesting these enzymes may operate extracellularly and under very alkaline conditions, both of which are highly unusual for P450 enzymes. This project will involve expressing these enzymes and analysing their activity under the high pH and low oxygen conditions of the gut environment. We will then engineer them by ancestral sequence reconstruction (ASR) to identify thermostable and more pH-neutral forms of the PE-degrading P450s to develop a system in which these enzymes can be used for breakdown of microplastics in wastes.

  • How did koalas evolve to exist entirely on eucalyptus leaves, which are toxic to most mammals?

    The diet of koalas is unique in comprising effectively 100% eucalyptus leaves, which contain a variety of toxic terpenes. Despite the interest in koala conservation and many years of study, we still do not understand how koalas can exist on such a this toxic diet. However a clue has come in the sequencing of the koala genome: compared to other marsupials and mammals more generally, koalas show a dramatic expansion in the CYP2C subfamily of cytochrome P450 enzymes. P450s are regarded as responsible for the metabolism of dietary and other environmental xenobiotics, so we hypothesise that the CYP2C forms in koalas have expanded to deal with the terpenes present in their diet and can oxidise these chemicals to facilitate their clearance from the koala’s circulation.

    This project will test this hypothesis by synthesising the CYP2C enzymes from koalas then expressing them in E. coli with the extant reductase accessory enzyme. We will determine how well the recombinant enzymes metabolise cineole and other eucalyptus terpenes. In so doing, we hope to answer a fundamental question about the biology of this iconic Australian animal, and one that has implications for koala conservation.

    If the hypothesis is proven to be correct (i.e. the extant koala CYP2C forms metabolise terpenes), selected ancestors of these CYP2C enzymes will be inferred, reconstructed and expressed to determine how the ability to metabolise eucalyptus terpenes arose during koala evolution, a model of how proteins evolve new functions.

  • Engineering a sustainable source of strigolactone hormones to improve food security across the world.

    Strigolactones (SLs) are a class of plant hormones that control many traits important for agriculture including shoot and root architecture, nutrient uptake and responses to parasitic weeds. Parasitic weeds stimulated by plant-derived SLs are widespread in arable lands of many developing countries and have devastating impacts on food production. Application of synthetic SLs to infested soils would provide a way to clear arable land of parasitic weeds and greatly enhance food security in the third world. Biotechnological sources of natural or chemically modified SLs would also improve agricultural crop yield and reduce manual labour costs in horticultural industries. The overall objective of this project is to develop means for SL production in biofactories and to improve the potency of synthetic and/or biofactory/engineered SLs. We will do so by analysing the evolution of naturally occurring SL-synthesising enzymes and leveraging ancestral sequence reconstruction to engineer robust novel 'designer' enzymes with specific desired activities.

  • Crystallisation of thermostable ancestral cytochrome P450 enzymes

    We have developed ancestral P450 enzymes that are extremely thermostable compared to modern enzymes, 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. Key to this is obtaining crystal structures of the enzymes to determine why they are more stable.

    We have already obtained crystals of a number of different thermostable P450s so this project would allow a student to make accelerated progress towards the goal of obtaining a structure for high impact publications that would be of great interest to industry as well as the field of protein structural biology and engineering.

  • Scaling up cytochrome P450-mediated biocatalysis for industry

    We have developed ancestral P450 enzymes that 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. This synthetic biology project is part of a collaboration with the Danish Technocal University and the multinational drug company, AstraZeneca, to further engineer these enzymes to be stable to oxidising conditions that currently limit reaction scale-up. It would suit students with a biochemistry, molecular biology or biochemical/process engineering background. A competitive UQ-DTU scholarship is currently open to support this project which would involve the succesful student spending some time in Copenhagen.

  • Synthetic biology of P450s for clean, green, solar-powered chemistry in drug development, bioremediation and biosensors

    We have developed ancestral P450 enzymes that 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 such biocatalytic processes can be made cheaper and more sustainable. In particular, we can replace the requirement for an expensive redox cofactor (NADPH) by linking the P450s to photosynthesis, to power P450 reactions for clean, green biocatalysis in microalgae.

    This synthetic biology project would suit a student with a biochemistry, molecular biology, plant biology or biochemical engineering background and will be undertaken in collaboration with the pharmaceutical company, AstraZeneca.

Supervision history

Current supervision

  • Doctor Philosophy

    Nano-bioreactors for sustainable biopolymer production

    Principal Advisor

  • 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

  • Doctor Philosophy

    Evolution of cytochrome P450 enzymes in response to dietary and environmental chemicals

    Principal Advisor

    Other advisors: Dr Gabriel Foley

  • Doctor Philosophy

    Nano-scale bioreactors: Protein cages as reusable scaffolds for designer enzymes

    Principal Advisor

  • Doctor Philosophy

    Development of Cytochrome P450 Enzymes as Biocatalysts for Metabolite and Novel Drug Candidate Synthesis for the Pharmaceutical Industry.

    Principal Advisor

Completed supervision

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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