Title
Discovery, biosynthesis and bioengineering of antibiotics from Gram-negative bacteria
Abstract
The overwhelming majority of antibiotics in clinical use are natural products or semi-synthetic derivatives produced by soil bacteria and filamentous fungi. Pathogenic microorganisms are becoming increasingly resistant to these compounds, and there is an urgent need to discover novel antibiotics to address the emerging health threat this poses. In this lecture, the discovery and biosynthetic elucidation of antibiotic natural products from underexplored Gram-negative bacterial genera will be discussed, 1, 2 and the development of bioengineering approaches for the production of novel analogues with enhanced activity will be described. In particular, the focus will be on polyketide antibiotics with potent activity against important antibiotic-resistant pathogens such as Mycobacterium tuberculosis and Acinetobacter baumannii.
1. 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. Discovery and biosynthesis of gladiolin: a Burkholderia gladioli antibiotic with promising activity against Mycobacterium tuberculosis. J. Am. Chem. Soc. 2017, 139, 7974-7981.
2. 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. Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases. Nat. Chem. Biol. 2018, 14, DOI: 10.1038/NCHEMBIO.2549
Biography
Professor Greg Challis graduated with a BSc in Chemistry (1994) from Imperial College London and a DPhil in Organic Chemistry (1998) from the University of Oxford, for research carried out under the supervision of Prof. Sir Jack Baldwin FRS. He carried out postdoctoral research as a Wellcome Trust International Prize Travelling Research Fellow in the Department of Chemistry at Johns Hopkins University, USA, with Prof. Craig Townsend (1998-2000) and in the Department of Genetics at John Innes Centre, UK, with Prof. Keith Chater FRS (2000-2001). In 2001 he took up a lectureship in Chemical Biology in the Department of Chemistry at the University of Warwick.
Prof Challis has published more than 110 papers on the chemistry and biology of bioactive natural products that have collectively received just short of 12,000 citations, and has delivered 170 invited lectures at international conferences, universities and research institutes. He is the recipient of several awards and prizes including the Gabor Medal (2009) and a Wolfson Research Merit Award (2013-2018) from the Royal Society, the 2017 Interdiscplinary Prize and 2009 Hickinbottom Award of the Royal Society of Chemistry, the 2007 Fleming Prize Lecture of the Society for General Microbiology, the 2007 Wain Medal Lecture of the University of Kent, the 2002 Meldola Medal and Prize of the Royal Society of Chemistry and the 1998 GlaxoWellcome Postdoctoral Fellowship. In 2011, he was elected as a Fellow of the Royal Society of Chemistry (FRSC) and a Fellow of the Royal Society of Biology (FRSB).