Leung Research Group at the University of Melbourne

We are part of the School of Chemistry and the Bio21 Molecular Science and Biotechnology Institute at the University of Melbourne.

We conduct multidisciplinary research, drawing on the fields of chemistry, biochemistry, biophysical chemistry, enzymology, molecular biology and structural biology, to understand the complex relationships between protein structure, function and modulation. Our goal is to utilise the knowledge that we generate to help solve some of the world’s most urgent challenges.

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Our Research

The Leung Research Group focuses on the enzymology that involves in protein function modulation. We apply a range of biophysical, chemical biology and structural biology techniques to enable our discoveries.

Metabolic regulation of protein functions

The ability to maintain homeostasis is critical to all forms of life. One mechanism through which this is achieved is the fine-tuning of cellular enzyme activities. In our group, we study how posttranslational modifications and metabolites affect the structure, activity and function of proteins and enzymes. These allow us to understand how different biochemical pathways signal and interact with one another to maintain stability in response to stress conditions. We are currently studying the enzymes that are involved in the regulation of carbon metabolism in Mycobacterium tuberculosis to understand how the pathogen survives inside the infected host with limited nutrients. Another system that we are studying is the plant ethylene-forming enzyme. We are presently investigating the mechanisms and structures of the different enzyme isoforms with a view to developing a detailed understanding of their roles in plant growth and development.

Enzyme technology for bioremediation

Enzymes are highly efficient catalysts that speed up chemical transformations under mild conditions. In our group, we study how we could harness the incredible catalytic prowess of enzymes as green biocatalysts to degrade environmental pollutants. We are especially interested in laccases, a class of multi-copper oxidase enzymes that catalyze one-electron oxidation of aromatic amine and phenolic substrates. Currently, we are studying how laccases mediate the degradation of organic pollutants at a molecular level to understand their mechanisms of catalysis. We also characterize the degradation products under different reaction conditions to investigate plausible degradation pathways.

Inhibitor discovery strategies and applications

The ability to modulate the activity of enzymes using natural or synthetic compounds has enormous potential in areas such as medicine. An important step in the early stages of inhibitor development is the identification and characterization of ligands that bind to the target. Our laboratory specializes in the application of biophysical techniques, especially NMR spectroscopy, for ligand screening and to study protein-ligand interactions and enzyme inhibition. A current interest is the development of inhibitors for lipid A phosphoethanolamine transferases. Such compounds have potential to be used as adjuvants to reverse bacterial resistance to polymyxins, a class of last-line antibiotics to treat multidrug-resistant infections.

Journal Articles

73
Eurtivong, C.; Leung, E.; Sharma, N.; Leung, I. K. H.; Reynisson, J. Phosphatidylcholine-Specific Phospholipase C as a Promising Drug Target. Molecules 2023, 28, 5637. DOI: 10.3390/molecules28155637

72
Huang, E. Y.-W.; Kwai, B. X. C.; Bhusal, R. P.; Bashiri, G.; Leung, I. K. H. Mycobacterium tuberculosis Rv1916 is an Acetyl-CoA-Binding Protein. ChemBioChem 2023, 24, e202300162. DOI: 10.1002/cbic.202300162

71
Zhang, S.; De Leon Rodriguez, L. M.; Li, F. F.; Huang, R.; Leung, I. K. H.; Harris, P.; Brimble. M. A. A Novel Tyrosine Hyperoxidation Enables Selective Peptide Cleavage. Chem. Sci. 2022, 13, 2753–2763. DOI: 10.1039/D1SC06216F

70
Shishodia, S.; Demetriades, M.; Zhang, D.; Tam, N. Y.; Maheswaran, P.; Clunie-O’Connor, C.; Tumber, A.; Leung, I. K. H.; Ng, Y. M.; Leissing, T. M.; El-Sagheer, A. H.; Salah, E.; Brown, T.; Aik, W. S.; McDonough, M. A.; Schofield, C. J. Structure-Based Design of Selective Fat Mass and Obesity Associated Protein (FTO) Inhibitors. J. Med. Chem. 2021, 64, 16609–16625. DOI: 10.1021/acs.jmedchem.1c01204

69
Sharma, N.; Leung, I. K. H. Novel Thermophilic Bacterial Laccase for the Degradation of Aromatic Organic Pollutants. Front. Chem. 2021, 9, 711345. DOI: 10.3389/fchem.2021.711345

68
Sharma, N.; Leung, I. K. H. Characterisation and Optimisation of a Novel Laccase from Sulfitobacter indolifex for the Decolourisation of Organic Dyes. Int. J. Biol. Macromol. 2021, 190, 574–584. DOI: 10.1016/j.ijbiomac.2021.09.003

67
Leung, E.; Patel, J.; Hollywood, J. A.; Zafar, A.; Tomek, P.; Barker, D.; Pilkington, L. I.; van Rensburg, M.; Langley, R. J.; Helsby, N. A.; Squire, C. J.; Baguley, B. C.; Denny, W. A.; Reynisson, J.; Leung, I. K. H. Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs. Oncol. Ther. 2021, 9, 541–556. DOI: 10.1007/s40487-021-00158-0

66
Mbenza, N. M.; Nasarudin, N.; Vadakkedath, P. G.; Patel, K.; Ismail, A. Z.; Hanif, M.; Wright, L. J.; Sarojini, V.; Hartinger, C. G.; Leung, I. K. H. Carbon Monoxide is an Inhibitor of HIF Prolyl Hydroxylase Domain 2. ChemBioChem 2021, 22, 2521–2525. DOI: 10.1002/cbic.202100181

65
Mak, O. W.; Sharma, N.; Reynisson, J.; Leung, I. K. H. Discovery of Novel Hsp90 C-Terminal Domain Inhibitors that Disrupt Co-Chaperone Binding. Bioorg. Med. Chem. Lett. 2021, 38, 127857. DOI: 10.1016/j.bmcl.2021.127857

64
Sharma, N.; Langley, R. J.; Eurtivong, C.; Leung, E.; Dixon, R. J.; Paulin, E. K.; Rees, S. W. P.; Pilkington, L. I.; Barker, D.; Reynisson, J.; Leung, I. K. H. An Optimised MALDI-TOF Assay for Phosphatidylcholine-Specific Phospholipase C. Anal. Methods 2021, 13, 491–496. DOI: 10.1039/D0AY02208J

63
Kwai, B. X. C.; Collins, A. J.; Middleditch, M. J.; Sperry, J.; Bashiri, G.; Leung, I. K. H. Itaconate is a Covalent Inhibitor of the Mycobacterium tuberculosis Isocitrate Lyase. RSC Med. Chem. 2021, 12, 57–61. DOI: 10.1039/D0MD00301H

62
Correddu, D.; Sharma, N.; Kaur, S.; Varnava, K. G.; Mbenza, N. M.; Sarojini, V.; Leung, I. K. H. An Investigation into the Effect of Ribosomal Protein S15 Phosphorylation to its Intermolecular Interactions by Using Phosphomimetic Mutant. Chem. Commun. 2020, 56, 7857–7860. DOI: 10.1039/D0CC01618G

61
McLarin, M.-A.; Leung, I. K. H. Substrate Specificity of Polyphenol Oxidase. Crit. Rev. Biochem. Mol. Biol. 2020, 55, 274–308. DOI: 10.1080/10409238.2020.1768209

60
Pilkington, L. I.; Sparrow, K.; Rees, S. W. P.; Paulin, E. K.; van Rensburg, M.; Xu, C. S.; Langley, R. J.; Leung, I. K. H.; Reynisson, J.; Leung, E.; Barker, D. Development, Synthesis and Biological Investigation of a Novel Class of Potent PC-PLC Inhibitors. Eur. J. Med. Chem. 2020, 191, 112162. DOI: 10.1016/j.ejmech.2020.112162

59
Mohan, A.; Hadi, J.; Gutierrez-Maddox, N.; Li, Y.; Leung, I. K. H.; Gao, Y.; Shu, Q.; Quek, S.-Y. Sensory, Microbiological and Physicochemical Characterisation of Functional Manuka Honey Yogurts Containing Probiotic Lactobacillus reuteri DPC16. Foods 2020, 9, 106. DOI: 10.3390/foods9010106

58
Eurtivong, C.; Pilkington, L. I.; van Rensburg, M.; White, R. M.; Brar, H. K.; Rees, S.; Paulin, E. K.; Xu, C. S.; Sharma, N.; Leung, I. K. H.; Leung, E.; Barker, D.; Reynisson, J. Discovery of Novel Phosphatidylcholine-Specific Phospholipase C Drug-like Inhibitors as Potential Anticancer Agents. Eur. J. Med. Chem. 2020, 187, 111919. DOI: 10.1016/j.ejmech.2019.111919

57
Correddu, D.; Montaño López, J. d. J.; Angermayr, S. A.; Middleditch, M. J.; Payne, L. S.; Leung, I. K. H. Effect of Consecutive Rare Codons on the Recombinant Production of Human Proteins in Escherichia coli. IUBMB Life 2020, 72, 266–274. DOI: 10.1002/iub.2162

56
Khomenko, T. M.; Zakharenko, A. L.; Chepanova, A. A.; Ilina, E. S.; Zakharova, O. D.; Kaledin, V. I.; Nikolin, V. P.; Popova, N. A.; Korchagina, D. V.; Reynisson, J.; Chand, R.; Ayine-Tora, D. M.; Patel, J.; Leung, I. K. H.; Volcho, K. P.; Salakhutdinov, N. F.; Lavrik, O. I. Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy. Int. J. Mol. Sci. 2020, 21, 126. DOI: 10.3390/ijms21010126

55
Mak, O. W.; Chand, R.; Reynisson, J.; Leung, I. K. H. Identification of Isoform-Selective Ligands for the Middle Domain of Heat Shock Protein 90 (Hsp90). Int. J. Mol. Sci. 2020, 20, 5333. DOI: 10.3390/ijms20215333

54
Filimonov, A. S.; Chepanova, A. A.; Luzina, O. A.; Zakharenko, A. L.; Zakharova, O. D.; Ilina, E. S.; Dyrkheeva, N. S.; Kuprushkin, M. S.; Kolotaev, A. V.; Khachatryan, D. S.; Patel, J.; Leung, I. K. H.; Chand, R.; Ayine‐Tora, D. M.; Reynisson, J.; Volcho, K. P.; Salakhutdinov, N. F.; Lavrik, O. I. New Hydrazinothiazole Derivatives of Usnic Acid as Potent Tdp1 Inhibitors. Molecules 2019, 24, 3711. DOI: 10.3390/molecules24203711

53
Bhusal, R. P.; Jiao, W.; Kwai, B. X. C.; Reynisson, J.; Collins, A. J.; Sperry, J.; Bashiri, G.; Leung, I. K. H. Acetyl-CoA-Mediated Activation of Mycobacterium tuberculosis Isocitrate Lyase 2. Nat. Commun. 2019, 10, 4639. DOI: 10.1038/s41467-019-12614-7

52
Li, Y.; McLarin, M.-A.; Middleditch, M. J.; Morrow, S. J.; Kilmartin, P. A.; Leung, I. K. H. An Approach to Recombinantly Produce Mature Grape Polyphenol Oxidase. Biochimie 2019, 165, 40–47. DOI: 10.1016/j.biochi.2019.07.002

51
Chepanova, A. A.; Mozhaitsev, E. S.; Munkuev, A. A.; Suslov, E. V.; Korchagina, D. V.; Zakharova, O. D.; Zakharenko, A. L.; Patel, J.; Ayine-Tora, D. M.; Reynisson, J.; Leung, I. K. H.; Volcho, K. P.; Salakhutdinov, N. F.; Lavrik, O. I. The Development of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors. Combination of Monoterpene and Adamantine Moieties via Amide or Thioamides Bridges. Appl. Sci. 2019, 9, 2767. DOI: 10.3390/app9132767

50
Correddu, D.; Montaño López, J. d. J.; Vadakkedath, P. G.; Lai, A.; Pernes, J. I.; Watson, P. R.; Leung, I. K. H. An Improved Method for the Heterologous Production of Soluble Human Ribosomal Proteins in Escherichia coli. Sci. Rep. 2019, 9, 8884. DOI: 10.1038/s41598-019-45323-8

49
Correddu, D.; Leung, I. K. H. Targeting mRNA Translation in Parkinson’s Disease. Drug Discov. Today 2019, 24, 1295–1303. DOI: 10.1016/j.drudis.2019.04.003

48
Mozhaitsev, E. S.; Zakharenko, A. L.; Suslov, E. V.; Korchagina, D. V.; Zakharova, O. D.; Vasil’eva, I. A.; Chepanova, A. A.; Black, E.; Patel, J.; Chand, R.; Reynisson, J.; Leung, I. K. H.; Volcho, K. P.; Salakhutdinov, N. F.; Lavrik, O. I. Novel Inhibitors of DNA Repair Enzyme TDP1 Combining Monoterpenoid and Adamantane Fragments. Anti-Cancer Agents Med. Chem. 2019, 19, 463–472. DOI: 10.2174/1871520619666181207094243

47
Zakharenko, A. L.; Luzina, O. A.; Sokolov, D. N.; Kaledin, V. I.; Nikolin, V. P.; Popova, N. A.; Patel, J.; Zakharova, O. D.; Chepanova, A. A.; Zafar, A.; Reynisson, J.; Leung, E.; Leung, I. K. H.; Volcho, K. P.; Salakhutdinov, N. F.; Lavrik, O. I. Novel Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Enhance the Therapeutic Impact of Topoteсan on In Vivo Tumor Models. Eur. J. Med. Chem. 2019, 161, 581–593. DOI: 10.1016/j.ejmech.2018.10.055

46
Son, S. J.; Huang, R.; Squire, C. J.; Leung, I. K. H. MCR-1: A Promising Target for Structure-Based Design of Inhibitors to Tackle Polymyxin Resistance. Drug Discov. Today 2019, 24, 206–216. DOI: 10.1016/j.drudis.2018.07.004

45
Abboud, M. I.; Chowdhury, R.; Leung, I. K. H.; Lippl, K.; Loenarz, C.; Claridge, T. D. W.; Schofield, C. J. Studies on the Substrate Selectivity of the Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Catalytic Domain. ChemBioChem 2018, 19, 2262–2267. DOI: 10.1002/cbic.201800246

44
Li-Zhulanov, N. S.; Zakharenko, A. L.; Chepanova, A. A.; Patel, J.; Zafar, A.; Volcho, K. P.; Salakhutdinov, N. F.; Reynisson, J.; Leung, I. K. H.; Lavrik, O. I. A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold. Molecules 2018, 23, 2468. DOI: 10.3390/molecules23102468

43
Zhang, S.; De Leon Rodriguez, L. M.; Huang, R.; Leung, I. K. H.; Harris, P. W. R.; Brimble, M. A. Total Synthesis of the Proposed Structure of Talarolide A. Org. Biomol. Chem. 2018, 16, 5286–5293. DOI: 10.1039/C8OB01230J

42
McAllister, T. E.; Yeh, T.-L.; Abboud, M. I.; Leung, I. K. H.; Hookway, E. S.; King, O. N. F.; Bhushan, B.; Williams, S. T.; Hopkinson, R. J.; Muenzel, M.; Loik, N. D.; Chowdhury, R.; Oppermann, U.; Claridge, T. D. W.; Goto, Y.; Suga, H.; Schofield, C. J.; Kawamura, A. Non-Competitive Cyclic Peptides for Targeting Enzyme-Substrate Complexes. Chem. Sci. 2018, 9, 4569–4578. DOI: 10.1039/C8SC00286J

41
Abboud, M. I.; McAllister, T. E.; Leung, I. K. H.; Chowdhury, R.; Jorgensen, C.; Domene, C.; Mecinović, J.; Lippl, K.; Hancock, R. L.; Hopkinson, R. J.; Kawamura, A.; Claridge, T. D. W.; Schofield, C. J. 2-Oxoglutarate Regulates Binding of Hydroxylated Hypoxia-Inducible Factor to Prolyl Hydroxylase Domain 2. Chem. Commun. 2018, 54, 3130–3133. DOI: 10.1039/c8cc00387d

40
Zhang, S.; De Leon Rodriguez, L. M.; Leung, I. K. H.; Cook, G. M.; Harris, P. W.; Brimble, M. A. Total Synthesis and Conformational Study of Callyaerin A: Anti-Tubercular Cyclic Peptide Bearing a Rare Rigidifying (Z)-2,3-Diaminoacrylamide Moiety. Angew. Chem. Int. Ed. 2018, 57, 3631–3635. DOI: 10.1002/anie.201712792

39
Mbenza, N. M.; Vadakkedath, P. G.; McGillivray, D. J.; Leung, I. K. H. NMR Studies of the Non-Haem Fe(II) and 2-Oxoglutarate-Dependent Oxygenases. J. Inorg. Biochem. 2017, 177, 384–394. DOI: 10.1016/j.jinorgbio.2017.08.032

38
Li, Y.; Zafar, A.; Kilmartin, P. A.; Reynisson, J.; Leung, I. K. H. Development and Application of an NMR-Based Assay for Polyphenol Oxidases. ChemistrySelect 2017, 2, 10435–10441. DOI: 10.1002/slct.201702144

37
Bhusal, R. P.; Patel, K.; Kwai, B. X. C.; Swartjes, A.; Bashiri, G.; Reynisson, J.; Sperry, J.; Leung, I. K. H. Development of NMR and Thermal Shift Assays for the Evaluation of Mycobacterium tuberculosis Isocitrate Lyase Inhibitors. Med. Chem. Commun. 2017, 8, 2155–2163. DOI: 10.1039/C7MD00456G

36
Yeh, T.-L.; Leissing, T. M.; Abboud, M. I.; Thinnes, C. C.; Atasoylu, O.; Holt-Martyn, J. P.; Zhang, D.; Tumber, A.; Lippl, K.; Lohans, C. T.; Leung, I. K. H.; Morcrette, H.; Clifton, I. J.; Claridge, T. D. W.; Kawamura, A.; Flashman, E.; Lu, X.; Ratcliffe, P. J.; Chowdhury, R.; Pugh, C. W.; Schofield, C. J. Molecular and Cellular Mechanisms of HIF Prolyl Hydroxylase Inhibitors in Clinical Trials. Chem. Sci. 2017, 8, 7651–7668. DOI: 10.1039/C7SC02103H

35
Bhusal, R. P.; Bashiri, G.; Kwai, B. X. C.; Sperry, J.; Leung, I. K. H. Targeting Isocitrate Lyase for the Treatment of Latent Tuberculosis. Drug Discov. Today 2017, 22, 1008–1016. DOI: 10.1016/j.drudis.2017.04.012

34
Santoso, B.; Yanaranop, P.; Kang, H.; Leung, I. K. H.; Jin, J. A Critical Update on the Synthesis of Carboxylated Polymers of Intrinsic Microporosity (C-PIMs). Macromolecules 2017, 50, 3043–3050. DOI: 10.1021/acs.macromol.7b00344

33
Kong, C. H. Z.; Leung, I. K. H.; Sarojini, V. Synthetic Insect Antifreeze Peptides Modify Ice Crystal Growth Habit. CrystEngComm 2017, 19, 2163–2167. DOI: 10.1039/C7CE00232G

32
Huang, R.; Bonnichon, A.; Claridge, T. D. W.; Leung, I. K. H. Protein-Ligand Binding Affinity Determination by the WaterLOGSY Method: An Optimised Approach Considering Ligand Rebinding. Sci. Rep. 2017, 7, 43727. DOI: 10.1038/srep43727

31
Hanauer, T.; Hopkinson, R. J.; Patel, K.; Li, Y.; Correddu, D.; Kawamura, A.; Sarojini, V.; Leung, I. K. H.; Gruber, T. Selective Recognition of the Di/Trimethylammonium Motif by an Artificial Carboxycalixarene Receptor. Org. Biomol. Chem. 2017, 15, 1100–1105. DOI: 10.1039/C6OB02616H

30
Harris, P. W. R.; Cook, G. M.; Leung, I. K. H.; Brimble, M. A. An Efficient Chemical Synthesis of Lassomycin Enabled by an On-Resin Lactamisation/Off-Resin Methanolysis Strategy and Preparation of Chemical Variants. Aust. J. Chem. 2017, 70, 172–183. DOI: 10.1071/CH16499

29
Young, P. G.; Yosaatmadja, Y.; Harris, P. W. R.; Leung, I. K. H.; Baker, E. N.; Squire, C. J. Harnessing Ester Bond Chemistry for Protein Ligation. Chem. Commun. 2017, 53, 1502–1505. DOI: 10.1039/C6CC09899A

28
Huang, R.; Ayine-Tora, D. M.; Muhammad Rosdi, M. N.; Li, Y.; Reynisson, J.; Leung, I. K. H. Virtual Screening and Biophysical Studies Lead to HSP90 Inhibitors. Bioorg. Med. Chem. Lett. 2017, 27, 277–281. DOI: 10.1016/j.bmcl.2016.11.059

27
Zhang, S.; De Leon Rodriguez, L. M.; Lacey, E.; Piggott, A. M.; Leung, I. K. H.; Brimble, M. A. Cyclisation of Linear Tetrapeptides Containing N-Methylated Amino Acids Using 2-Propanephosphonic Acid Anhydride. Eur. J. Org. Chem. 2017, 2017, 149–158. DOI: 10.1002/ejoc.201601016

26
Lindsay, A. C.; Leung, I. K. H.; Sperry, J. Synthesis of the Azepinobisindole Alkaloid Iheyamine A Enabled by a Cross-Mannich Reaction. Org. Lett. 2016, 18, 5404–5407. DOI: 10.1021/acs.orglett.6b02798

25
Chowdhury, R.; Leung, I. K. H.; Tian, Y.-M.; Abboud, M. I.; Ge, W.; Domene, C.; Cantrelle, F.-X.; Landrieu, I.; Hardy, A. P.; Pugh, C. W.; Ratcliffe, P. J.; Claridge, T. D. W.; Schofield, C. J. Structural Basis for Oxygen Degradation Domain Selectivity of the HIF Prolyl Hydroxylases. Nat. Commun. 2016, 7, 12673. DOI: 10.1038/ncomms12673

24
Huang, R.; Leung, I. K. H. Protein-Directed Dynamic Combinatorial Chemistry: A Guide to Protein Ligand and Inhibitor Discovery. Molecules 2016, 21, 910. DOI: 10.3390/molecules21070910

23
Khan, A.; Leśniak, R. K.; Brem, J.; Rydzik, A. M.; Choi, H.; Leung, I. K. H.; McDonough, M. A.; Schofield, C. J.; Claridge, T. D. W. Development and Application of Ligand-Based NMR Screening Assays for γ-Butyrobetaine Hydroxylase. Med. Chem. Commun. 2016, 7, 873–880. DOI: 10.1039/C6MD00004E

22
Hopkinson, R. J.; Leung, I. K. H.; Smart, T. J.; Rose, N. R.; Henry, L.; Claridge, T. D. W.; Schofield, C. J. Studies on the Glutathione-Dependent Formaldehyde-Activating Enzyme from Paracoccus denitrificans. PLoS ONE 2015, 10, e0145085. DOI: 10.1371/journal.pone.0145085

21
Chan, M. C.; Atasoylu, O.; Hodson, E.; Tumber, A.; Leung, I. K. H.; Chowdhury, R.; Gómez-Pérez, V.; Demetriades, M.; Rydzik, A. M.; Holt-Martyn, J.; Tian, Y.-M.; Bishop, T.; Claridge, T. D. W.; Kawamura, A.; Pugh, C. W.; Ratcliffe, P. J.; Schofield, C. J. Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases With Activity in the Murine Brain. PLoS ONE 2015, 10, e0132004. DOI: 10.1371/journal.pone.0132004

20
Tarhonskaya, H.; Chowdhury, R.; Leung, I. K. H.; Loik, N. D.; McCullagh, J. S. O.; Claridge, T. D. W.; Schofield, C. J.; Flashman, E. Investigating the Contribution of the Active Site Environment to the Slow Reaction of Hypoxia-Inducible Factor Prolyl Hydroxylase Domain 2 With Oxygen. Biochem. J. 2014, 463, 363–372. DOI: 10.1042/BJ20140779

19
Rydzik, A. M.; Leung, I. K. H.; Kochan, G. T.; McDonough, M. A.; Claridge, T. D. W.; Schofield, C. J. Oxygenase-Catalyzed Desymmetrization of N,N-Dialkyl-Piperidine-4-Carboxylic Acids. Angew. Chem. Int. Ed. 2014, 53, 10925–10927. DOI: 10.1002/anie.201406125

18
Scotti, J. S.; Leung, I. K. H.; Ge, W.; Bentley, M. A.; Paps, J.; Kramer, H. B.; Lee, J.; Aik, W.; Choi, H.; Paulsen, S. M.; Bowman, L. A. H.; Loik, N. D.; Horita, S.; Ho, C.-h.; Kershaw, N. J.; Tang, C. M.; Claridge, T. D. W.; Preston, G. M.; McDonough, M. A.; Schofield, C. J. Human Oxygen Sensing May Have Origins in Prokaryotic Elongation Factor Tu Prolyl-Hydroxylation. Proc. Natl. Acad. Sci. U.S.A. 2014, 111, 13331–13336. DOI: 10.1073/pnas.1409916111

17
Rydzik, A. M.; Leung, I. K. H.; Kochan, G. T.; Loik, N. D.; Henry, L.; McDonough, M. A.; Claridge, T. D. W.; Schofield, C. J. Comparison of the Substrate Selectivity and Biochemical Properties of Human and Bacterial γ-Butyrobetaine Hydroxylase. Org. Biomol. Chem. 2014, 12, 6354–6358. DOI: 10.1039/C4OB01167H

16
Tarhonskaya, H.; Szöllössi, A.; Leung, I. K. H.; Bush, J. T.; Henry, L.; Chowdhury, R.; Iqbal, A.; Claridge, T. D. W.; Schofield, C. J.; Flashman, E. Studies on Deacetoxycephalosporin C Synthase Support a Consensus Mechanism for 2-Oxoglutarate Dependent Oxygenases. Biochemistry 2014, 53, 2483–2493. DOI: 10.1021/bi500086p

15
Lingard, H.; Han, J. T.; Thompson, A. L.; Leung, I. K. H.; Scott, R. T. W.; Thompson, S.; Hamilton, A. D. Diphenylacetylene-Linked Peptide Strands Induce Bidirectional β-Sheet Formation. Angew. Chem. Int. Ed. 2014, 53, 3650–3653. DOI: 10.1002/anie.201309353

14
Tarhonskaya, H.; Rydzik, A. M.; Leung, I. K. H.; Loik, N. D.; Chan, M. C.; Kawamura, A.; McCullagh, J. S. O.; Claridge, T. D. W.; Flashman, E.; Schofield, C. J. Non-Enzymatic Chemistry Enables 2-Hydroxyglutarate-Mediated Activation of 2-Oxoglutarate Oxygenases. Nat. Commun. 2014, 5, 3423. DOI: 10.1038/ncomms4423

13
Rydzik, A. M.; Leung, I. K. H.; Thalhammer, A.; Kochan, G. T.; Claridge, T. D. W.; Schofield, C. J. Fluoromethylated Derivatives of Carnitine Biosynthesis Intermediates – Synthesis and Applications. Chem. Commun. 2014, 50, 1175−1177. DOI: 10.1039/C3CC47581F

12
Bush, J. T.; Walport, L. J.; McGouran, J. F.; Leung, I. K. H.; Berridge, G.; van Berkel, S. S.; Basak, A.; Kessler, B. M.; Schofield, C. J. The Ugi Four-Component Reaction Enables Expedient Synthesis and Comparison of Photoaffinity Probes. Chem. Sci. 2013, 4, 4115−4120. DOI: 10.1039/C3SC51708J

11
van Berkel, S. S.; Nettleship, J. E.; Leung, I. K. H.; Brem, J.; Choi, H.; Stuart, D. I.; Claridge, T. D. W.; McDonough, M. A.; Owens, R. J.; Ren, J.; Schofield, C. J. Binding of (5S)-Penicilloic Acid to Penicillin Binding Protein 3. ACS Chem. Biol. 2013, 8, 2112–2116. DOI: 10.1021/cb400200h

10
Leung, I. K. H.; Demetriades, M.; Hardy, A. P.; Lejeune, C.; Smart, T. J.; Szöllössi, A.; Kawamura, A.; Schofield, C. J.; Claridge, T. D. W. Reporter Ligand NMR Screening Method for 2-Oxoglutarate Oxygenase Inhibitors. J. Med. Chem. 2013, 56, 547–555. DOI: 10.1021/jm301583m

9
Henry, L.; Leung, I. K. H.; Claridge, T. D. W.; Schofield, C. J. γ-Butyrobetaine Hydroxylase Catalyses a Stevens Type Rearrangement. Bioorg. Med. Chem. Lett. 2012, 22, 4975–4978. DOI: 10.1016/j.bmcl.2012.06.024

8
Rose, N. R.; Woon, E. C.; Tumber, A.; Walport, L. J.; Chowdhury, R.; Li, X. S.; King, O. N. F.; Lejeune, C.; Ng, S. S.; Krojer, T.; Chan, M. C.; Rydzik, A. M.; Hopkinson, R. J.; Che, K. H.; Daniel, M.; Strain-Damerell, C.; Gileadi, C.; Kochan, G.; Leung, I. K. H.; Dunford, J.; Yeoh, K. K.; Ratcliffe, P. J.; Burgess-Brown, N.; von Delft, F.; Muller, S.; Marsden, B.; Brennan, P. E.; McDonough, M. A.; Oppermann, U.; Klose, R. J.; Schofield, C. J.; Kawamura, A. The Plant Growth Regulator Daminozide Is a Selective Inhibitor of the Human KDM2/7 Histone Demethylases. J. Med. Chem. 2012, 55, 6639–6643. DOI: 10.1021/jm300677j

7
Rydzik, A. M.; Leung, I. K. H.; Kochan, G. T.; Thalhammer, A.; Oppermann, U.; Claridge, T. D. W.; Schofield, C. J. Development and Application of a Fluoride-Detection-Based Fluorescence Assay for γ-Butyrobetaine Hydroxylase. ChemBioChem 2012, 13, 1559–1563. DOI: 10.1002/cbic.201200256

6
Demetriades, M.; Leung, I. K. H.; Chowdhury, R.; Chan, M. C.; McDonough, M. A.; Yeoh, K. K.; Tian, Y.-M.; Claridge, T. D. W.; Ratcliffe, P. J.; Woon, E. C. Y.; Schofield, C. J. Dynamic Combinatorial Chemistry Employing Boronic Acids/Boronate Esters Leads to Potent Oxygenase Inhibitors. Angew. Chem. Int. Ed. 2012, 51, 6672–6675. DOI: 10.1002/anie.201202000

5
Rotili, D.; Altun, M.; Kawamura, A.; Wolf, A.; Fischer, R.; Leung, I. K. H.; Mackeen, M. M.; Tian, Y.-M.; Ratcliffe, P. J.; Mai, A.; Kessler, B. M.; Schofield, C. J. A Photoreactive Small-Molecule Probe for 2-Oxoglutarate Oxygenases. Chem. Biol. 2011, 18, 642–654. DOI: 10.1016/j.chembiol.2011.03.007

4
Leung, I. K. H.; Brown Jr, T.; Schofield, C. J.; Claridge, T. D. W. An Approach to Enzyme Inhibition Employing Reversible Boronate Ester Formation. Med. Chem. Commun. 2011, 2, 390–395. DOI: 10.1039/C1MD00011J

3
Chowdhury, R.; Yeoh, K. K.; Tian, Y.-M.; Hillringhaus, L.; Bagg, E. A.; Rose, N. R.; Leung, I. K. H.; Li, X. S.; Woon, E. C. Y.; Yang, M.; McDonough, M. A.; King, O. N.; Clifton, I. J.; Klose, R. J.; Claridge, T. D. W.; Ratcliffe, P. J.; Schofield, C. J. ; Kawamura, A. The Oncometabolite 2-Hydroxyglutarate Inhibits Histone Lysine Demethylases. EMBO Rep. 2011, 12, 463–469. DOI: 10.1038/embor.2011.43

2
Leung, I. K. H.; Krojer, T. J.; Kochan, G. T.; Henry, L.; von Delft, F.; Claridge, T. D. W.; Oppermann, U.; McDonough, M. A.; Schofield, C. J. Structural and Mechanistic Studies on γ-Butyrobetaine Hydroxylase. Chem. Biol. 2010, 17, 1316–1324. DOI: 10.1016/j.chembiol.2010.09.016

1
Leung, I. K. H.; Flashman, E.; Yeoh, K. K.; Schofield, C. J.; Claridge, T. D. W. Using NMR Solvent Water Relaxation to Investigate Metalloenzyme–Ligand Binding Interactions. J. Med. Chem. 2010, 53, 867–875. DOI: 10.1021/jm901537q

Book Chapters

3
Chan, Y. Y.; Mbenza, N. M.; Chan, M. C.; Leung, I. K. H. Assays to Study Hypoxia-Inducible Factor Prolyl Hydroxylase Domain 2 (PHD2), a Key Human Oxygen Sensing Protein. In Methods in Molecular Biology; Weinert, E. E., Ed.; Oxygen Sensing, Methods and Protocol; Humana: New York, NY, 2023; Vol. 2648, Chapter 12, pp 187–206. DOI: 10.1007/978-1-0716-3080-8_12

2
Huang, R.; Leung, I. K. H. Protein–Small Molecule Interactions by WaterLOGSY. In Methods in Enzymology; Wand, A. J., Ed.; Biological NMR Part B; Academic Press: Cambridge, MA, 2019; Vol. 615, Chapter 14, pp 477–500. DOI: 10.1016/bs.mie.2018.08.020

1
Xiang, L.-W.; Melton, L. D.; Leung, I. K. H. Interactions of β-Lactoglobulin With Small Molecules. In Encyclopedia of Food Chemistry; Melton, L., Shahidi, F., Varelis, P., Eds.; Elsevier: Amsterdam, 2019; Vol. 2, pp 560–565. DOI: 10.1016/B978-0-08-100596-5.21488-1

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Dr Ivanhoe Leung

Senior Lecturer in Biological Chemistry

Dr Ivanhoe Leung is a Senior Lecturer in Biological Chemistry at the University of Melbourne. He attained his undergraduate and doctorate degrees in Chemistry and received postdoctoral training at the University of Oxford. In 2014, he joined the University of Auckland as a Lecturer in Chemical Biology. He was promoted to Senior Lecturer in 2017, and to Senior Lecturer (over the bar) in 2019. Dr Leung was recruited to the University of Melbourne through the Driving Research Momentum scheme in 2021. His current interests include (1) mechanistic enzymology, in particular the understanding of the complex relationships between protein structure, function, and modulation, (2) enzyme technology, especially the use of enzymes as biocatalysts for bioremediation, and (3) inhibitor discovery.

As an emerging leader in biological chemistry research, Dr Leung has authored over 70 publications and 3 book chapters. His work has been cited over 3000 times, and he has an h-index of 30. Dr Leung’s research has been recognised by several awards, most notably the prestigious University of Auckland Early Career Research Excellence Award in 2019, and the Selby Research Award for outstanding academic research in 2021.

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Brief CV

The University of Melbourne
▪ 2021 –
      ▪ Senior Lecturer in Biological Chemistry, School of Chemistry
      ▪ Group Leader, Bio21 Molecular Science & Biotechnology Institute

The University of Auckland
▪ 2021 –
      ▪ Honorary Academic, School of Chemical Sciences
▪ 2019 – 2021
      ▪ Senior Lecturer (over the bar), School of Chemical Sciences
▪ 2017 – 2019
      ▪ Senior Lecturer, School of Chemical Sciences
▪ 2014 – 2017
      ▪ Lecturer in Chemical Biology, School of Chemical Sciences

University of Oxford
▪ 2012 – 2014
      ▪ Postdoctoral research assistant, Department of Chemistry
▪ 2008 – 2013
      ▪ D.Phil Organic Chemistry, Department of Chemistry and St Peter’s College
▪ 2003 – 2007
      ▪ M.Chem Chemistry, Department of Chemistry and St Peter’s College

Awards

▪ 2021: Selby Research Award, Selby Scientific Foundation
▪ 2019: Early Career Research Excellence Award, The University of Auckland
▪ 2019: JSPS Hope Fellow, Japan Society for the Promotion of Science

Memberships

Melbourne University Chemical Society (MUCS)
▪ 2023 –
      ▪ President

RACI Green and Sustainable Chemistry (GASC) National Group
▪ 2022 –
      ▪ Committee Member

Maurice Wilkins Centre for Molecular Biodiscovery
▪ 2019 – 2021
      ▪ Associate Investigator

Centre for Green Chemical Science, The University of Auckland
▪ 2018 – 2021
      ▪ Co-Deputy Director
▪ 2015 – 2017
      ▪ Committee Member

New Zealand Institute of Chemistry (NZIC) Auckland Branch
▪ 2020
      ▪ Chemistry Education Group Representative
▪ 2019
      ▪ Chair
▪ 2016 – 2018
      ▪ Treasurer
▪ 2015
      ▪ Committee Member

New Zealand Society for Biochemistry and Molecular Biology (NZSBMB)
▪ 2015 – 2020
      ▪ Auckland Representative

Journal Editing

Frontiers in Chemistry
▪ 2022 –
      ▪ Associate Editor, Green and Sustainable Chemistry Section

Scientific Reports
▪ 2018 –
      ▪ Editorial Board Member

Evelyn Huang

PhD candidate

Evelyn completed her Master of Industrial Research in Chemistry at the University of Melbourne, where she collaborated with industry in a project to manage volatile organic compounds in paint systems. Her current project involves the protein-level regulation of Mycobacterium tuberculosis isocitrate lyase.

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Francis Kuang

PhD candidate

Francis completed his Master of Drug Discovery and Development at the Victoria University of Wellington. In his MDDD project, Francis developed a genomic driven approach to identify biosynthetically gifted actinomycetes from New Zealand mangrove samples. His current project aims to decipher the mechanism and regulation of 1-aminocyclopropane-1-carboxylic acid oxidase.

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Kallet Zhou

MSc candidate

Kallet received his Bachelor’s degree in Medical Chemistry at the University of Melbourne. In 2021, Kallet worked as a research assistant working in Shenzhen Bay Laboratory in the field of biosynthesis. His current project involves the study of Mycobacterium tuberculosis isocitrate dehydrogenase and its modulation.

Benjamin Harris

MSc candidate

Benjamin completed his Bachelor of Science degree in Chemistry at the university of Melbourne in 2022. His MSc research, which is conducted jointly with the laboratory of Dr Brad Clarke, involves investigating the potential of enzymatic degradation of the environmental contaminant PFAS.

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Patrick Bajan

BScH candidate

Patrick completed his Bachelor of Science at Monash University in 2022 majoring in both Chemistry and Biochemistry. His current project involves understanding the characteristic mutations involved in the functional shift towards medium-chain alkyl-sulfate ester oxidation of Rv3406 in Mycobacterium tuberculosis.

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Anu Sharma

Visitor

Anu is a visiting PhD student from the School of Chemical Sciences of the University of Auckland (Sarojini Group). During her visit, she will conduct protein NMR experiments to investigate the binding interactions between antiviral peptides and their target protein.

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Huong Le

Visitor

Le Viet Lan Huong is a visiting PhD student from Matsuda Lab, School of Life Science and Technology, Tokyo Institute of Technology. During the visit, she will work on a project that utilize laccase to mediate the degradation of organic pollutants.

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Past members

Postdoctoral Research Fellow

▪ Dr Brooke Kwai, 2022
▪ Dr Aimee Son, 2019

Doctor of Philosophy – PhD

▪ Dr Vicky Juan, 2023
▪ Dr Renjie Huang, 2023
▪ Dr Brooke Kwai, 2022
▪ Dr Eva Antony, 2022
▪ Dr Nabangshu Sharma, 2021
▪ Dr Ryan Dixon, 2021 (co-supervisor)
▪ Dr Naasson Mbambi Mbenza, 2020
▪ Dr Jinal Patel, 2020
▪ Dr Dona Gunawardana, 2020
▪ Dr Praveen George Vadakkedath, 2020 (co-supervisor)
▪ Dr Oi Wei Mak, 2020
▪ Dr Danilo Correddu, 2019
▪ Dr Ram Bhusal, 2018 (co-supervisor)
▪ Dr Yu Li, 2017

Master of Science – MSc

▪ Jinpeng Zhou, 2023
▪ Junlang Zhong, 2023
▪ Simran Kaur, 2019
▪ Renjie Mike Huang, 2017

Bachelor of Science (Honours) – BScH

▪ Mark-Anthony McLarin, 2019
▪ Brooke Kwai, 2017
▪ Nawal Nasarudin, 2016
▪ Dona Gunawardana, 2016
▪ M. Nasri Muhammad Rosdi, 2015

Postgraduate Diploma in Science – PGDipSci

▪ Weijing Sun, 2020
▪ Renjie Mike Huang, 2015

Summer Research Scholars

▪ Sarah Tynan, 2023
▪ Tricia Lee, 2022
▪ Daniel Bousfield, 2020
▪ José de Jesús Montaño López, 2018
▪ Jane Pernes, 2017
▪ Johanna Viluma, 2017
▪ Amy Lai, 2017
▪ Paris Watson, 2016

Undergraduate Project Students

▪ YuTao Zhou, 2022
▪ Devia Rachmat Kurniawan, 2022

Visitor

▪ Dr Tianyang Liu, 2023
▪ Cathy Yin, 2020
▪ Misha van Merrienboer, 2019
▪ Esmée Van Tol, 2019
▪ Ravi Tej Allam, 2017
▪ Thomas Hanauer, 2015

• Brooke’s PhD Thesis Submission and Lorne Proteins 2022

  Congratulations Brooke for submitting her PhD thesis for examination on the 28th of January. Brooke studied Mycobacterium tuberculosis isocitrate lyase during her PhD and she did some exciting NMR and structural work. It has not been easy for her in the last few years so it is a great achievement! Well done! Brooke also managed to join us at the Lorne …

  6 February, 2022 Conference, Sem...
• Welcome Tricia (AMGEN Scholar)

  We welcome Tricia Lee, currently an undergraduate student at the University of Queensland, to join our lab over the summer through the AMGEN Scholar programme. The programme kicked off today at Queen's College Melbourne with an insightful fire lighting ceremony from an indigenous elder. Welcome Tricia and hope you will enjoy the research that you will conduct over the next …

  5 January, 2022 Group Member
• 2021 Christmas Lunch

  We celebrated a tough year with a nice Christmas lunch today (with the Melbourne-based group). 2021 has been tough, especially during the ~16 weeks of lockdowns when we cannot go to the lab. Thanks everyone for your help in setting up the lab and for your energy, enthusiasm & hard work! Have a great break!

  22 December, 2021 Group Member
• 16th FAOBMB Congress

  We attended at the 16th FAOBMB Congress, which was held online this year due to the COVID-19 pandemic. Ivan gave an oral presentation on ethylene synthesis (work that was conducted by Dona, Simran et al.), and Brooke and Vicky gave poster presentations about their work. The online conference was very enjoyable, which showcased some excellent science from Australia, New Zealand, …

  25 November, 2021 Conference, Sem...
• Back to the lab + Welcome Evelyn to join the team

  We are delighted to return to the research laboratory today after a 13-week long COVID-19 lockdown. We also welcome the latest member of our group, Evelyn Huang, who joined us as a PhD graduate researcher during lockdown. Evelyn completed her Master of Industrial Research in Chemistry at the University of Melbourne. She will work on the regulation of Mycobacterium tuberculosis …

  4 November, 2021 University of M...
• Eva’s PhD Thesis Submission

  Congratulations Eva for submitting her PhD thesis for examination today. Eva joined us in November 2017. Her PhD focused on the application of biophysical and biochemical techniques to study protein-ligand interactions and enzyme inhibition. Eva worked on a diverse range of projects during her PhD. Of particular highlights are (1) experimentally validating the use of molecular descriptors to pre-filter virtual libraries …

  30 October, 2021 Group Member
• Virtual Seminar at North Carolina State University

  Ivan gave a virtual seminar at the Department of Molecular and Structural Biochemistry of North Carolina State University this morning. Ivan covered several topics in the seminar, including our work on bacterial enzymes that are involved in infectious disease, the use of chemical biology tools to identify and validate enzyme targets in glioma cells, and our progress on harnessing enzyme …

  29 October, 2021 Conference, Sem...
• New Paper in Frontiers of Chemistry

  Congratulations Dr Nabangshu Sharma for his new paper in Frontiers of Chemistry (Impact factor: 5.221). This is Nabangshu’s second “first author” paper in as many months. The paper describes Nabangshu’s studies of a novel thermophilic laccase from Geobacillus yumthangensis, and its potential as a biocatalyst to degrade organic pollutants. This is an invited paper and it is part of the …

  20 October, 2021 Publication

More News

Opportunities and Funding

Postdoctoral Research

Currently, we do not have any positions available. Applicants who wish to apply for their own funding may contact Dr Leung for informal enquiries.

PhD Studies

Informal enquiries regarding PhD studies can be made to Dr Ivanhoe Leung by email.

The University of Melbourne has strict entry requirements for the PhD program, which can be found on the University website.

Information about weighted average mark (WAM) can be found on the website here.

PhD students are typically funded by the University of Melbourne Graduate Research Scholarship, Melbourne Research Scholarship, or the Research Training Program Scholarship. Information about scholarships at the University of Melbourne can be found on the dedicated University website here.

MSc (Chemistry) and BSc (Honours) Studies

We are keen to have Melbourne undergraduates to carry out their fourth year or Master’s research projects in our group. Please contact Dr Ivanhoe Leung by email for further information.

Summer Projects

Our laboratory participates in the Amgen Scholars Program. Please follow the website here for further information.

Contact Details

Bio21 Molecular Science & Biotechnology Institute
The University of Melbourne
30 Flemington Rd
Melbourne
VIC 3010

Email: ivanhoe.leung@unimelb.edu.au
Twitter: @Leung_Group

Useful Links and Information

▪ School of Chemistry
▪ Bio21 Molecular Science & Biotechnology Institute
▪ Doctor of Philosophy – Science
▪ Master of Science (Chemistry)
▪ Master of Philosophy – Science
▪ Scholarships at the University of Melbourne