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Greg Challis


Prof Greg Challis

Monash Warwick Alliance Professor of Sustainable Chemistry (Chemical and Synthetic Biology)




Research Summary

Natural products chemistry and biology, including isolation and structure determination of new bioactive natural products, genomics and genetics of natural product biosynthesis, enzymology and structural biology of natural product biosynthesis, chemical synthesis of bioactive natural products and intermediates in their biosynthesis, genetic manipulation of bioactive natural product biosynthesis pathways to produce new analogues, molecular mechanism of action of bioactive natural products and their biological function. A highly multidisciplinary approach to these problems is taken encompassing high field NMR spectoscopy, mass spectrometry, HPLC, organic synthesis, bioinformatics, microbiological methods, molecular genetic manipulation, recombinant protein overproduction and purification, enzyme assay development, X-ray crystallography, protein NMR spectroscopy and single particle cryo-EM.

Selected Recent Publications
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.
Discovery and biosynthesis of gladiolin: a Burkholderia gladioli antibiotic with promising activity against Mycobacterium tuberculosis. L. Song, M. Jenner, J. Masschelein, C. Jones, M. Bull, S. Harris, R. Hartkoorn, A. Vocat, I. Romero-Canelón, P. Coupland, Paul, G. Webster, M. Dunn, R. Weiser, C. Paisey, S. Cole, J. Parkhill, E. Mahenthiralingam and G.L. Challis. J. Am. Chem. Soc. 2017, 139, 7974-7981.
A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units. L. Ray, T.R. Valentic, T. Miyazawa, D.M. Withall, L. Song, J.C. Milligan, H. Osaka, S. Takahashi, S.-C. Tsai and G.L. Challis. Nat. Commun. 2016, 7, 13609.
A flavin-dependent decarboxylase-dehydrogenase-monooxygenase assembles the warhead of α, β-epoxyketone proteasome inhibitors. D. Zabala, J.W. Cartwright, D.M. Roberts, B.J.C. Law, L. Song, M. Samborskyy, P.F. Leadlay, J. Micklefield, and G.L. Challis. J. Am. Chem. Soc. 2016, 138, 4342-4345.
Discovery of microbial natural products by activation of silent biosynthetic gene clusters. P.J. Rutledge and G.L. Challis. Nat. Rev. Microbiol. 2015, 13, 509-523.
Stereochemistry and mechanism of undecylprodigiosin oxidative carbocyclization to streptorubin B by the Rieske oxygenase RedG. D.M. Withall, S.W. Haynes and G.L. Challis. J. Am. Chem. Soc. 2015, 137, 7889-7897.