Monash Warwick Alliance Professor of Sustainable Chemistry (Chemical and Synthetic Biology)
We work on the discovery, biosynthesis, bioengineering, and mechanism of action of antibiotics and other bioactive metabolites produced by bacteria.
Groups at Warwick
- Challis Group
- Warwick Integrative Synthetic Biology Centre
- Warwick Antimicrobial Interdisciplinary Centre
- Midlands Integrative Biosciences Training Partnership (BBSRC DTP)
- Interdisciplinary Biomedical Research Doctoral Training Partnership (MRC DTP)
- Centre for Doctoral Training in Synthetic Biology (EPSRC CDT)
- Monash Biomedicine Discovery Institute
- Australian Research Council Centre of Excellence for Innovations in Protein and Peptide Science
- Monash Warwick Alliance Professor of Sustainable Chemistry (Chemical and Synthetic Biology), Department of Chemistry, University of Warwick and Department of Biochemistry and Molecular Biology Monash University (2016-)
- Professor of Chemical Biology, Department of Chemistry, University of Warwick (2006-2016)
- Senior Lecturer/Reader in Chemical Biology, Department of Chemistry, University of Warwick (2003-2006)
- Lecturer in Chemical Biology, Department of Chemistry, University of Warwick (2001-2003)
- Wellcome Trust research fellow, Department of Genetics, John Innes Centre (2000-2001)
- Wellcome Trust research fellow, Department of Chemistry, Johns Hopkins University (1998-2000)
- DPhil in Organic Chemistry, University of Oxford (1998)
- BSc in Chemistry, Imperial College London (1994)
My research focuses on the chemistry and biology of microbial natural products. This encompasses natural product discovery, elucidation of biosynthetic pathways, creation of natural product analogues and novel molecular scaffolds via synthetic biology, and the mechanism of action and biological function of natural products.
Our approach is highly interdisciplinary and employs numerous complementary techniques, including chemical synthesis and analysis, molecular genetic manipulation, enzymology, protein mass spectrometry, structural biology (X-ray crystallography, protein NMR spectroscopy and single particle cryo-electron microscopy), bioinformatics, molecular modelling, and bioactivity assays.
I teach Bioorganic Chemistry (CH3F5 - year 3) and Organic Chemistry (tutorials and workshops in years 1 and 2)
I am supervising the following Postdoctoral Research Fellows:
- Lona Alkhalaf (Senior Research Fellow)
- Doug Roberts (Research Fellow)
- Angelo Gallo (Research Fellow)
- Chuan Huang (Research Fellow)
- Shanshan Zhou (Research Fellow)
- Chris Fage (Research Fellow)
- Arun Gupta (Research Fellow)
- Xinyun Jian (Research Fellow)
- Jinlian Zhao (Research Fellow)
I am supervising the following PhD students:
- Matthew Beech
- Ioanna Nakou
- Jacob Sargeant
- Helen Smith
- Fang Pang
- Rebecca Clayton
- Marlene Rothe
- Munro Passmore
I am supervising the following MRes students:
- Charles Hinchliffe
I am supervising the following MChem students:
- Sacha Charlton
- Callum Bullock
Selected recent publications:
Molecular basis for control of antibiotic production by a bacterial hormone. S. Zhou, H. Bhukya, N. Malet, P. Harrison, D. Rea, M.J. Belousoff, H. Venugopal, P.K. Sydor, K.M. Styles, L. Song, M.J. Cryle, L.M. Alkhalaf, V. Fülöp, G.L. Challis and C. Corre. Nature, 2021, 590, 463-467.
Structures of a non-ribosomal peptide synthetase condensation domain suggest the basis of substrate selectivity. T. Izoré, Y.T.C. Ho, J.A. Kaczmarski, A. Gavriilidou, K.H. Chow, D.L. Steer, R.J.A. Goode, R.B. Schittenhelm, J. Tailhades, M. Tosin, G.L. Challis, E.H. Krenske, N. Ziemert, C.J. Jackson and M.J. Cryle. Nat. Commun. 2021, 12, 2511.
Genomics-driven discovery of a novel glutarimide antibiotic from Burkholderia gladioli reveals an unusual polyketide synthase chain release mechanism. I.T. Nakou, M. Jenner, Y. Dashti, I. Romero-Canelón, J. Masschelein, E. Mahenthiralingam and G.L. Challis. Angew. Chem. Int. Ed. 2020, 59, 23145-23153.
Discovery and biosynthesis of bolagladins: unusual lipodepsipeptides from Burkholderia gladioli clinical isolates. Y. Dashti, I.T. Nakou, A.J. Mullins, G. Webster, X. Jian, E. Mahenthiralingam and G.L. Challis. Angew. Chem. Int. Ed. 2020, 59, 21553-21561.
The catalytic mechanism of aromatic nitration by cytochrome P450 TxtE: Involvement of a ferric-peroxynitrite intermediate. S. Louka, S.M. Barry, D.J. Heyes, M.Q.E. Mubarak, H.S. Ali, L.M. Alkhalaf, A.W. Munro, N.S. Scrutton, G.L. Challis and S.P. de Visser. J. Am. Chem. Soc. 2020, 142, 15764-15779.
Developmentally regulated volatiles geosmin and 2-methylisoborneol attract a soil arthropod to Streptomyces bacteria promoting spore dispersal. P. G. Becher, V. Verschut, M.J. Bibb, M.J. Bush, B.P. Molnár, E. Barane, M.M. Al-Bassam, G. Chandra, L. Song, G.L. Challis, M.J. Buttner, and K. Flärdh. Nat. Microbiol. 2020, 5, 821-829.
A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis. J. Masschelein, P.K. Sydor, C. Hobson, R. Howe, C. Jones, D.M. Roberts, Z.L. Yap, J. Parkhill, E. Mahenthiralingam and G.L. Challis. Nat. Chem. 2019, 11, 906-912.
Structural basis for chain release from the enacyloxin polyketide synthase. S. Kosol, A. Gallo, D. Griffiths, T.R. Valentic, J. Masschelein, M. Jenner, E.L. de los Santos, L. Manzi, P.K. Sydor, D. Rea, S. Zhou, V. Fülöp, N.J. Oldham, S.-C. Tsai, G.L. Challis, and J.R. Lewandowski. Nat. Chem. 2019, 11, 913-923.
Genome mining identifies cepacin as a key plant-protective metabolite of the biopesticidal bacterium Burkholderia ambifaria. A.J. Mullins, J.A.H. Murray, M.J. Bull, M. Jenner, C. Jones, G. Webster, T.R. Connor, J. Parkhill, G.L. Challis and E. Mahenthiralingam. Nat. Microbiol. 2019, 4, 996-1005.
Binding of distinct substrate conformations enables hydroxylation of remote sites in thaxtomin D by cytochrome P450 TxtC. L.M. Alkhalaf, S.M. Barry, D. Rea, A. Gallo, D. Griffths, J.R. Lewandoswki, V. Fulop and G.L. Challis. J. Am. Chem. Soc. 2019, 141, 216-222.
Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases. M. Jenner, S. Kosol , D. Griffiths, P. Prasongpholchai, L. Manzi, A.S. Barrow, J.E. Moses, N.J. Oldham, J.R. Lewandowski and G.L. Challis. Nat. Chem. Biol. 2018, 14, 270-275.