BEACON Team

Professor Steven Kelly

Professor of Microbial Genetics and Molecular Biology

S.L.Kelly@swansea.ac.uk

Swansea University

Background

Professor Steven Kelly was born in Cardiff and studied in the newly founded Genetics Department in Swansea until 1983 undertaking his BSc and a PhD involving yeast genetics. He learned yeast genetic engineering with Paul Nurse and gained a Lectureship in Sheffield University Krebs Institute, moving to a Chair at Aberystwyth in 1997 where he was lead for molecular biology and Director of the Wolfson Laboratory of Cytochrome P450 Biodiversity. In 2004 he moved to Swansea University to act as Chair of Research during the period of early establishment of the School of Medicine and the building of the Institute of Life Science and led the Biomedical Sciences submission in RAE 2008 to a 2.65 score.

Research Interests

Professor Kelly has acted on the International Advisory Board for several conferences and has chaired two international symposia in Swansea in 2005 and 2006. He continues to work closely with industry that has included BP, Shell, GSK, Pfizer, Novartis, Bristol Myers Squibb, Zeneca, Syngenta, BASF, Bayer, Viamet, Mars, Foundation for Water Research and has supervised eleven CASE research studentships. Research in Swansea has been supported by the research councils and FP6. He is Swansea PI on a National Institutes of Health (USA) Programme Grant (2004- ) with M Waterman at Vanderbilt concerning P450 functional genomics in streptomycetes, that was renewed in 2008 and recently obtained a second on antifungal drug resistance with D. Rogers in Memphis. Current interests include molecular microbial research, functional genomics, translational medical microbiology and chemical biology research with over three hundred publications.

BEACON Activities

  • Swansea Science Director

  • Member of Swansea Local Management Group

Future Plans

Exploit microbial use of biomass to produce chemical entities of use to industry and pharma.

Recent Publications

Sewell TR, Hawkins NJ, Stotz HU, Huang YJ, Kelly SL, Kelly DE, Fraaije B, Fitt BDL. Azole sensitivity in Leptosphaeria pathogens of oilseed rape: the role of lanosterol 14alpha-demethylase. Scientific Reports. 2017, 7:15849.

Butts A, DeJarnette C, Peters TL, Parker JE, Kerns ME, Eberle KE, Kelly SL, Palmer GE. Target abundance-based fitness screening (TAFiS) facilitates rapid identification of target-specific and physiologically active chemical probes. mSphere. 2017, DOI: 10.1128/mSphere.00379-17. 

Hull CM, Warrilow AGS, Rolley NJ, Price CL, Donnison IS, Kelly DE, Kelly SL. Co-production of 11alpha-hydroxyprogesterone and ethanol using recombinant yeast expressing fungal steroid hydroxylases. Biotechnol Biofuels. 2017, 10:226.

Rybak JM, Dicken CM, Parker JE, Caudle K, Manigaba K, Whaley SG, Nishimoto A, Luna-Tapia A, Roy S, Zhang Q, Barker KS, Palmer GE, Sutter TR, Homayouni R, Wiederhold NP, Kelly SL, Rogers PD. Loss of C-5 sterol desaturase activity results in increased resistance to azole abd echinocandin antifungals in a clinical isolate of Candida parapsilosis. Antimicrobial Agents and Chemotherapy. 2017, doi: 10.1128/AAC.00651-17.

Warrilow AGS, Parker JE, Price CL, Garvey EP, Hoekstra WJ, Schotzinger RJ, Wiederhold NP, Nes WD, Kelly DE, Kelly SL. The tetrazole VT-1161 is a potent inhibitor of Trichophyton rubrum through its inhibition T. rubrum CYP51. Antimicrobial Agents and Chemotherapy. 2017, EPub ahead of print.

Colley T, Alanio A, Kelly SL, Sehra G, Kizawa Y, Warrilow AGS, Parker JE, Kelly DE, Kimura G, Anderson-Dring L, Nakaoki T, Sunose M, Onions S, Crepin D, Lagasse F, Crittall M, Shannon J, Cooke M, Bretagne S, King-Underwood J, Murray J, Ito K, Strong P, Rapeport G. In vitro and in vivo antifungal profile of a novel and long acting inhaled azole PC945, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy. 2017, doi:10.1128/AAC.02280-16.

McCourt P, Liu H-Y, Parker JE, Gallo-Ebert C, Donigan M, Bata A, Giordano C, Kelly SL, Nickels Jr JT. Proper sterol distribution is required for Candida albicans hyphal formation and virulence. G3: Genes, Genomes, Genetics. 2016, doi: 10.1534/g3.116.033969.

Warrilow AG, Price CL, Parker JE, Rolley NJ, Smyrniotis CJ, Hughes DD, Thoss V, Nes WD, Kelly DE, Holman TR, Kelly SL. Azole antifungal sensitivity of sterol 14α-demethylase (CYP51) and CYP5218 from Malassezia globosa. Scientific Reports. 2016, 6, 27690.

Warrilow AG, Parker JE, Price CL, Nes WD, Garvey EP, Hoekstra WJ, Schotzinger RJ, Kelly DE, Kelly SL. The invesitgational drug VT-1129 is a highly potent inhibitor of Cryptococcus species CYP51 but only weakly inhibits the human enzyme. Antimicrobial Agents and Chemotherapy. 2016, 60(8), 4530-4538.

Warrilow AGS, Parker JE, Price CL, Nes WD, Kelly SL, Kelly DE. CYP51-mediated azole resistance in Aspergillus fumigatus: an in vitro biochemical study. Antimicrobial Agents and Chemotherapy. 2015, 59(12), 7771-7778.

Berkow El, Manigaba K, Parker JE, Barker KS, Kelly SL, Rogers PD. Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis. Antimicrobial Agents and Chemotherapy. 2015, 59(10), 5942-5950.

Derbyshire MC, Michaelson L, Parker J, Kelly S, Thacker U, Powers SJ, Bailey A, Hammond-Kosack K, Courbot M, Rudd J. Analysis of cytochrome b5 reductase-mediated metabolism in the phytopathogenic fungus Zymoseptoria tritici reveals novel functionalities implicated in virulence. Fungal Genetics and Biology. 2015, 82, 69-84.

Lamb DC, Warrilow AG, Rolley NJ, Parker JE, Nes WD, Smith SN, Kelly DE, Kelly SL. Azole antifungal agents to treat the human pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through inhibition of sterol 14alpha-demethylase (CYP51). Antimicrobial Agents and Chemotherapy. 2015, 59(8), 4707-4713.

Price CL, Parker JE, Warrilow AGS, Kelly DE, Kelly SL. Azole fungicides - understanding resistance mechanisms in agricultural fungal pathogens. Pest Management Science. 2015, 71(8), 1054-1058.

Price CL, Warrilow AGS, Parker JE, Mullins JGL, Nes WD, Kelly DE, Kelly SL. Novel substrate specificity and temperature sensitive activity of Mycosphaerella graminicola CYP51 (MgCYP51) supported by the native NADPH cytochrome P450 reductase (CPR). Applied and Environmental Microbiology. 2015, 81(10), 3379-3386.

Salvage R, Hull CM, Kelly DE, Kelly SL. Use of 70% alcohol for the routine removal of microbial hard surface bioburden in life science cleanrooms. Future Microbiology. 2014, 9(10), 1123-1130.

Hull CM, Loveridge EJ, Donnison IS, Kelly DE, Kelly SL. Co-production of bioethanol and probiotic yeast biomass from agricultural feedstock: application of the rural biorefinery concept. AMB Express. 2014, 4, Epub.

Hull CM, Loveridge EJ, Rolley NJ, Donnison IS, Kelly SL, Kelly DE. Co-production of ethanol and squalene using a Saccharomyces cerevisiae ERG1 (squalene epoxidase) mutant and agro-industrial feedstock. Biotechnology for Biofuels. 2014, 7, Epub.

Warrilow AGS, Hull CM, Parker JE, Garvey EP, Hoekstra WJ, Moore WR, Schotzinger RJ, Kelly DE, Kelly SL. The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme. Antimicrobial Agents and Chemotherapy. 2014, Epub.

Parker JE, Warrilow AGS, Price CL, Mullins JGL, Kelly DE, Kelly SL. Resistance to antifungals that target CYP51. Journal of Chemical Biology. 2014, 7(4), 143-161. 

Warrilow AGS, Hull CM, Rolley NJ, Parker JE, Nes WD, Smith SN, Kelly DE, Kelly SL. Clotrimazole as a potent agent for treating the oomycete fish pathogen Saprolegnia parasitica through inhibition of sterol 14alpha-demethylase (CYP51). Applied and Environmental Microbiology. 2014. 80(19), 6154-6166.

Hawkins NJ, Cools HJ, Sierotzki H, Shaw MW, Knogge W, Kelly SL, Kelly DE, Fraaije BA. Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance. Molecular Biology and Evolution. 2014, 31(7), 1793-1802.

Carter HE, Fraaije BA, West JS, Kelly SL, Mehl A, Shaw MW, Cools HJ. Alterations in the predicted regulatory and coding regions of the sterol 14alpha-demethylase gene (CYP51) confer decreased azole sensitivity in the oilseed rape pathogen Pyrenopeziza brassicae. Molecular Plant Pathology 2014, 15(5), 513-522.

Reid EL, Weynberg KD, Love J, Isupov MN, Littlechild JA, Wilson WH, Kelly SL, Lamb DC, Allen, MJ. Functional and structural characterisation of a viral cytochrome b5. FEBS Letters 2013, 587(22), 3633-3639.

Eddouzi J, Parker JE, Vale-Silva LA, Coste A, Ischer F, Kelly S, Manai M, Sanglard D. Molecular mechanisms of drug resistance in clinical Candida species isolated from Tunisian hospitals. Antimicrobial Agents and Chemotherapy. 2013, 57(7), 3182-3193.

Hoobler EK, Rai G, Warrilow AGS, Perry SC, Smyrniotis CJ, Jadhav A, Simeonov A, Parker JE, Kelly DE, Maloney DJ, Kelly SL, Holman TR. Discovery of a novel dual fungal CYP51/human 5-lipoxygenase inhibitor: implications for anti-fungal therapy. PLoS One. 2013, 8(6), e65928.

Belic A, Pompon D, Monostory K, Kelly D, Kelly S, Rozman, D. An algorithm for rapid computational construction of metabolic networks: A cholesterol biosynthesis example. Computers in Biology and Medicine. 2013, 43(5), 471-480.

Calabrese EC, Castellano S, Santoriello M, Sgherri C, Quartacci MF, Calucci L, Warrilow AGS, Lamb DC, Kelly SL, Milite C, Granata I, Sbardella G, Stefancich G,Maresca B, Porta A. Antifungal activity of azole compounds CPA18 and CPA109 against azole-susceptible and -resistant strains of Candida albicans. Journal of Antimicrobial Chemotherapy. 2013, 68(5), 1111-1119.

Fan JR, Urban M, Parker JE, Brewer HC, Kelly SL, Hammond-Kosack KE, Fraaije BA, Liu XL, Cools HJ. Characterization of the sterol 14 alpha-demethylases of Fusarium graminearum identifies a novel genus-specific CYP51 function. New Phytologist. 2013, 198(3), 821-835.

Parker JE, Warrilow AG, Cools HJ, Fraaije BA, Lucas JA, Rigdova K, Griffiths WJ, Kelly DE, Kelly SL. Prothioconazole and prothioconazole-desthio activity against Candida albicans sterol 14 alpha-demethylase (CaCYP51). Applied and Environmental Microbiology. 2013, 79(5), 1639-1645.

Kelly SL, Kelly DE. Microbial cytochromes P450: biodiversity and biotechnology. Where do cytochromes P450 come from, what do they do and what can they do for us? Philosophical Transactions of the Royal Society B 2013, 368(1612)SI, Art. No. 20120476.

Warrilow AG, Parker JE, Kelly DE, Kelly SL. Azole affinity of sterol 14 alpha-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens. Antimicrobial Agents and Chemotherapy. 2013, 57(3), 1352-1360.

Newsome AW, Nelson D, Corran A, Kelly SL, Kelly DE. The cytochrome P450 complement (CYPome) of Mycosphaerella graminicola. Biotechnology and Applied Biochemistry. 2013, 60(1), 52-64.

Hull CM, Bader O, Parker JE, Weig M, Gross U, Warrilow AG, Kelly DE, Kelly SL. Two clinical isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B both harbor mutations in ERG2. Antimicrobial Agents and Chemotherapy. 2012, 56(12), 6417-6421.

Hull CM, Parker JE, Bader O, Weig M, Gross U, Warrilow AG, Kelly DE, Kelly SL. Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance to azoles and amphotericin B. Antimicrobial Agents and Chemotherapy. 2012, 56(8), 4223-4232.

Zhao B, Moody SC, Hider RC, LeiL, Kelly SL, Waterman MR, Lamb DC. Structural Analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore Coelibactin. International Journal of Molecular Sciences. 2012, 13(7), 8500-8513.

Vale-SilvaLA, Coste AT, Ischer F, Parker JE, Kelly SL, Pinto E, Sanglard D. Azole resistance by loss of function of the sterol delta-5,6-desaturase gene (ERG3) in Candida albicans does not necessarily decrease virulence. Antimicrobial Agents and Chemotherapy. 2012, 56(4), 1960-1968.

Warrilow AGS, Mullins JGL, Hull CM, Parker JE, Lamb DC, Kelly DE, Kelly SL. S279 point mutations in Candida albicans sterol 14-alpha demethylase (CYP51) reduces in vitro inhibition by fluconazole. Antimicrobial Agents and Chemotherapy. 2012, 56(4), 2099-2107.

Moody SC, Zhao B, Lei L, Nelson DR, Mullins JG, Waterman MR, Kelly SL, Lamb DC. Investigating conservation of the albaflavenone biosynthetic pathway and CYP170 bifunctionality in streptomycetes. FEBS Journal. 2011, 279(9), 1640-1649.

Agnew CRJ, Warrilow AGS, Burton NM, Lamb DC, Kelly SL, Brady RL. An enlarged, adaptable active site in CYP164 family P450 enzymes, the sole P450 in Mycobacterium leprae. Antimicrobial Agents and Chemotherapy. 2012, 56(2), 391-402.

Higgins J, Pinjon E, Oltean HN, White TC, Kelly SL, Martel CM, Sullivan DJ, Coleman DC, Moran GP. Triclosan antagonizes fluconazole activity against Candida albicans. Journal of Dental Research 2012, 91(1), 65-70.

Cools HJ, Mullins JGL, Fraaije BA, Parker JE, Kelly DE, Lucas JA, Kelly SL. Impact of recently emerged sterol 14 alpha-demethylase (CYP51) variants of Mycosphaerella graminicola on azole fungicide sensitivity. Applied and Environmental Microbiology. 2011, 77(11), 3830-3837.

Parker JE, Warrilow AGS, Cools HJ, Martel CM, Nes, WD, Fraaije BA, Lucas JA, Kelly DE, Kelly SL. Mechanism of binding of prothioconazole to Mycosphaerella graminicola CYP51 differs from that of other azole antifungals. Applied and Environmental Microbiology. 2011, 77(4), 1460-1465.

Martel CM, Parker JE, Jackson CJ, Warrilow AGS, Rolley N, Greig C, Morris SM, Donnison IS, Kelly DE, Kelly SL. Expression of bacterial levanase in yeast enables simultaneous saccharification and fermentation of grass juice to bioethanol. Bioresource Technology. 2011, 102(2), 1503-1508.

Cheng Q, Lamb DC, Kelly SL, Lei L, Guengerich FP. Cyclization of a cellular dipentaenone by Streptomyces coelicolor cytochrome P450 154A1 without oxidation/reduction. Journal of the American Chemical Society 2010, 132(43), 15173-15175.

Martel CM, Parker JE, Bader O, Weig M, Gross U, Warrilow AGS, Rolley N, Kelly DE, Kelly SL. Identification and characterization of four azole-resistant erg3 mutants of Candida albicans. Antimicrobial Agents and Chemotherapy. 2010, 54(11), 4527-4533.

Martel CM, ParkerJE, Warrilow AGS, Rolley N, Kelly SL, Kelly, DE. Complementation of a Saccharomyces cerevisiae ERG11/CYP51 (sterol 14 alpha-demethylase) doxycycline-regulated mutant and screening of the azole sensitivity of Aspergillus fumigatus isoenzymes CYP51A and CYP51B. Antimicrobial Agents and Chemotherapy. 2010, 54(11), 4920-4923.

Warrilow AGS, Melo N, Martel CM, Parker JE, Kelly SL, Kelly DE. Expression, purification, and characterization of Aspergillus fumigatus sterol 14-alpha demethylase (CYP51) isoenzymes A and B. Antimicrobial Agents and Chemotherapy. 2010, 54(10), 4225-4234.

Warrilow AGS, Martel CM, Parker JE, Melo N, Lamb DC, Nes D, Kelly DE, Kelly SL. Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51). Antimicrobial Agents and Chemotherapy. 2010, 54(10), 4235-4245.

Martel CM, Parker JE, Bader O, Weig M, Gross U, Warrilow AGS, Kelly DE, Kelly SL. A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14 alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B. Antimicrobial Agents and Chemotherapy. 2010, 54(9), 3578-3583.

Cools HJ, Parker JE, Kelly DE, Lucas JA, Fraaije BA, Kelly SL. Heterologous expression of mutated eburicol 14 alpha-demethylase (CYP51) proteins of Mycosphaerella graminicola to assess effects on azole fungicide Sensitivity and intrinsic protein function. Applied and Environmental Microbiology. 2010, 76(9), 2866-2872.

Martel CM, Warrilow AGS, Jackson CJ, Mullins JGL, Togawa RC, Parker JE, Morris MS, Donnison IS, Kelly DE, Kelly SL. Expression, purification and use of the soluble domain of Lactobacillus paracasei beta-fructosidase to optimise production of bioethanol from grass fructans. Bioresource Technology. 2010, 101(12), 4395- 4402.

Lamb DC, Lei L, Zhao B, Yuan H, Jackson CJ, Warrilow AGS, Skaug T, Dyson PJ, Dawson ES, Kelly SL, Hachey DL, Waterman MR. Streptomyces coelicolor A3(2) CYP102 protein, a novel fatty acid hydroxylase encoded as a heme omain without an N-terminal redox partner. Applied and Environmental Microbiology. 2010, 76(6), 1975-1980.

Affiliations

Fellow of the Royal Society of Biology
Fellow of the Royal Society of Chemistry
Fellow of the Learned Society of Wales