Dr Andrew Warrilow

Penodiad Er Anrhydedd (Gwyddorau Dynol ac Iechyd)

Faculty of Medicine Health and Life Science

+44 (0) 1792 205678 ext 9138

a.warrilow@abertawe.ac.uk

Trosolwg

Mae Dr Andrew Warrilow yn fiocemegydd proteinau sy’n gweithio yng Nghanolfan Bioamrywiaeth Cytocrom P450

(http://www.p450swansea.co.uk/) yn Ysgol Feddygaeth Prifysgol Abertawe. Dechreuodd ei yrfa yn IACR Long Ashton Research Station ger Bryste ym 1995 cyn symud i Labordy Bioamrywiaeth Cytocrom P450 Wolfson ym Mhrifysgol Aberystwyth yn ystod 1998 i weithio gyda’r Athro Steven Kelly ac wedyn ymunodd â Phrifysgol Abertawe yn 2004.

Prif ddiddordebau ymchwil Andrew yw demethylases (CYP51) 14-alffa sterol pathogenau ffwngaidd a’u partneriaid rhydocs rhydwythas (CPR) cytocrom P450. CYP51 ffwngaidd yw ensym targed cyffuriau gwrth-ffwngaidd azole ac mae ymwrthedd cynyddol tuag at gyffuriau gwrth-ffwngaidd azole ymysg unigion clinigol Candida spp., Aspergillus spp. a Mucorales yn golygu bod angen gwell dealltwriaeth o fecanweithiau ymwrthedd azole a synthesis a phrosesau sgrinio cyfryngau therapiwtig newydd i oresgyn yr ymwrthedd cynyddol hwn.

Mae ei ddiddordebau ymchwil eraill yn cynnwys canfod nodweddion monoocsigenasau cytocrom P450 ewcaryotig a procaryotig, yn enwedig o ran rhwymo ligand, penodolrwydd swbstradau a chineteg ensymau; mae Andrew yn rhannu ei arbenigedd â myfyrwyr sydd wedi cofrestru ar y modiwlau a addysgir y mae’n cyfrannu atynt.

Mae Andrew yn gyd-archwilydd ar raglen Bioburo Canolfan Ragoriaeth BEACON (http://www.beaconwales.org). Mae BEACON yn bartneriaeth rhwng Prifysgolion Aberystwyth, Bangor ac Abertawe a Phrifysgol De Cymru sy’n gweithio ym maes trawsnewid biomas a biowastraff yn gynhyrchion bio gyda chymwysiadau masnachol. Mae BEACON yn brosiect gwerth £18.3 miliwn a gefnogir gan Gronfa Datblygu Rhanbarthol Ewrop drwy Lywodraeth Cymru a’r prif nod yw helpu busnesau Cymru i ymchwilio i gyfleoedd bio ar gyfer twf drwy ddarparu mynediad at gyfarpar arbenigol eang ac arbenigedd gwyddonol. Enillodd BEACON wobr RegioStars 2014 am y Prosiect Rhanbarthol gorau yn yr UE.

Meysydd Arbenigedd

• Demethylases (CYP51) sterol 14-alffa
• Rhydwythas Cytocrom P450 NADPH
• Sgrinio cyffuriau gwrth-ffwngaidd Azole
• Monoocsigenasau cytocrom P450
• Ensymoleg
• Puro proteinau
• Biocemeg proteinau

Uchafbwyntiau Gyrfa

Ymchwil

Mae ymwrthedd i gyffuriau gwrth-ffwngaidd azole a welwyd mewn heintiau ffwngaidd clinigol ymysg Candida spp., Aspergillus spp. a Mucorales yn broblem gynyddol sydd angen sylw brys.

Mae Andrew wedi cymryd rhan mewn sawl astudiaeth yn archwilio modd gweithredu biocemegol cyffuriau gwrth-ffwngaidd azole gydag ensym CYP51 targed pathogenau ffwngaidd a’r homolog dynol. Mae’r gwaith hwn wedi cynnwys canfod nodweddion dull gweithredu cyfryngau therapiwtig newydd yn cynnwys tetrazole VT-1161 (Viamet/Mycovia) a triazole PC945 (Pulmocide). Ar adeg ysgrifennu hwn (Mai 2020) mae yna dreialon Cam 3 yn cael eu cynnal ar VT-1161 a threialon Cam 2 ar PC945.

Mae ymchwiliadau eraill yn cynnwys y sail biocemegol sylfaenol ar gyfer ymwrthedd cynyddol azole mewn unigion clinigol Candida albicans ac Aspergillus fumigatus a briodolwyd yn flaenorol i amnewidion asidau amino yn yr ensym CYP51 ffwngaidd. Yn C. albicans mae effeithiau amnewidion asidau amino CYP51 unigol ar weithgarwch ensymau o ran goddefedd i fluconazole yn adiol, tra yn A. fumigatus gall amnewidion asidau amino unigol yn CYP51A roi goddefedd sylweddol i azole. At hyn, mae’r dull gweithredu biocemegol ar gyfer cyffuriau gwrth-ffwngaidd azole yn erbyn ensymau CYP51 o Cryptococcus spp., Trichophyton rubrum a Malassezia globosa wedi’i archwilio hefyd.

Bydd dealltwriaeth bellach o’r mecanweithiau dan sylw o ran ymwrthedd azole CYP51 yn llywio’r cynllun ar gyfer y genhedlaeth nesaf o gyfryngau therapiwtig er mwyn goresgyn yr ymwrthedd sy’n dod i’r amlwg i gyffuriau gwrth-ffwngaidd azole presennol.

Cydweithrediadau

Cyhoeddiadau

Uchafbwyntiau Ymchwil

Nie, D., Hoobler, E., Rai, G., Warrilow, A., Perry, S., Smyrniotis, C., Jadhav, A., Simeonov, A., Parker, J., Kelly, D., Maloney, D., Kelly, S., & Holman, T. (2013). Discovery of a Novel Dual Fungal CYP51/Human 5-Lipoxygenase Inhibitor: Implications for Anti-Fungal Therapy. PLoS ONE, 8(6)
https://doi.org/10.1371/journal.pone.0065928, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa15178
Warrilow, A., Hull, C., Rolley, N., Parker, J., Nes, W., Smith, S., Kelly, D., & Kelly, S. (2014). Clotrimazole as a Potent Agent for Treating the Oomycete Fish Pathogen Saprolegnia parasitica through Inhibition of Sterol 14 -Demethylase (CYP51). Applied and Environmental Microbiology, 80(19), 6154-6166.
https://doi.org/10.1128/AEM.01195-14, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa18616
Price, C., Parker, J., Warrilow, A., Kelly, D., & Kelly, S. (2015). Azole fungicides - understanding resistance mechanisms in agricultural fungal pathogens. Pest Management Science, n/a-n/a.
https://doi.org/10.1002/ps.4029, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa20922
Lamb, D., Warrilow, A., Rolley, N., Parker, J., Nes, W., Smith, S., Kelly, D., & Kelly, S. (2015). Azole Antifungal Agents To Treat the Human Pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through Inhibition of Sterol 14α-Demethylase (CYP51). Antimicrobial Agents and Chemotherapy, 59(8), 4707-4713.
https://doi.org/10.1128/AAC.00476-15, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa31514
http://aac.asm.org/content/59/8/4707.full.pdf+html
Warrilow, A., Price, C., Parker, J., Rolley, N., Smyrniotis, C., Hughes, D., Thoss, V., Nes, W., Kelly, D., Holman, T., & Kelly, S. (2016). Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa. Scientific Reports, 6(1)
https://doi.org/10.1038/srep27690, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa34335
Hull, C., Warrilow, A., Rolley, N., Price, C., Donnison, I., Kelly, D., & Kelly, S. (2017). Co-production of 11α-hydroxyprogesterone and ethanol using recombinant yeast expressing fungal steroid hydroxylases. Biotechnology for Biofuels, 10(1)
https://doi.org/10.1186/s13068-017-0904-z, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa37567
Zhou, W., Warrilow, A., Thomas, C., Ramos, E., Parker, J., Price, C., Vanderloop, B., Fisher, P., Loftis, M., Kelly, D., Kelly, S., & Nes, W. (2018). Functional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1863(10), 1164-1178.
https://doi.org/10.1016/j.bbalip.2018.07.004, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa41148
Warrilow, A., Nishimoto, A., Parker, J., Price, C., Flowers, S., Kelly, D., Rogers, P., & Kelly, S. (2019). The Evolution of Azole Resistance in Candida albicans Sterol 14α-Demethylase (CYP51) through Incremental Amino Acid Substitutions. Antimicrobial Agents and Chemotherapy, 63(5)
https://doi.org/10.1128/aac.02586-18, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa48946
Warrilow, A., Parker, J., Price, C., Rolley, N., Nes, W., Kelly, D., & Kelly, S. (2019). Isavuconazole and voriconazole inhibition of sterol 14α-demethylases (CYP51) from Aspergillus fumigatus and Homo sapiens. International Journal of Antimicrobial Agents
https://doi.org/10.1016/j.ijantimicag.2019.07.011, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa51096
Lamb, D., Follmer, A., Goldstone, J., Nelson, D., Warrilow, A., Price, C., True, M., Kelly, S., Poulos, T., & Stegeman, J. (2019). On the occurrence of cytochrome P450 in viruses. Proceedings of the National Academy of Sciences, 116(25), 12343-12352.
https://doi.org/10.1073/pnas.1901080116, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa50802
Colley, T., Sehra, G., Chowdhary, A., Alanio, A., Kelly, S., Kizawa, Y., Armstrong-James, D., Fisher, M., Warrilow, A., Parker, J., Kelly, D., Kimura, G., Nishimoto, Y., Sunose, M., Onions, S., Crepin, D., Lagasse, F., Crittall, M., Shannon, J...., & Rapeport, G. (2018). In Vitro and In Vivo Efficacy of a Novel and Long-Acting Fungicidal Azole, PC1244, on Aspergillus fumigatus Infection. Antimicrobial Agents and Chemotherapy, 62(5), AAC.01941-17
https://doi.org/10.1128/aac.01941-17, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa38876
http://dx.doi.org/10.1128/aac.01941-17
Colley, T., Alanio, A., Kelly, S., Sehra, G., Kizawa, Y., Warrilow, A., Parker, J., Kelly, D., Kimura, G., Anderson-Dring, L., Nakaoki, T., Sunose, M., Onions, S., Crepin, D., Lagasse, F., Crittall, M., Shannon, J., Cooke, M., Bretagne, S...., & Rapeport, G. (2017). In vitro and in vivo antifungal profile of a novel and long acting inhaled azole, PC945, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy, AAC.02280-16
https://doi.org/10.1128/AAC.02280-16, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa32189
Warrilow, A., Parker, J., Price, C., Garvey, E., Hoekstra, W., Schotzinger, R., Wiederhold, N., Nes, W., Kelly, D., & Kelly, S. (2017). The Tetrazole VT-1161 Is a Potent Inhibitor of Trichophyton rubrum through Its Inhibition of T. rubrum CYP51. Antimicrobial Agents and Chemotherapy, 61(7), e00333-17
https://doi.org/10.1128/AAC.00333-17, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa34176
Warrilow, A., Parker, J., Price, C., Nes, W., Garvey, E., Hoekstra, W., Schotzinger, R., Kelly, D., & Kelly, S. (2016). The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme. Antimicrobial Agents and Chemotherapy, 60(8), 4530-4538.
https://doi.org/10.1128/AAC.00349-16, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa29154
Warrilow, A., Hull, C., Parker, J., Garvey, E., Hoekstra, W., Moore, W., Schotzinger, R., Kelly, D., Kelly, S., & Hull, C. (2014). 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, 58(12), 7121-7127.
https://doi.org/10.1128/AAC.03707-14, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa18693
Price, C., Warrilow, A., Parker, J., Mullins, J., Nes, W., Kelly, D., Kelly, S., & Schottel, J. (2015). Novel Substrate Specificity and Temperature-Sensitive Activity of Mycosphaerella graminicola CYP51 Supported by the Native NADPH Cytochrome P450 Reductase. Applied and Environmental Microbiology, 81(10), 3379-3386.
https://doi.org/10.1128/AEM.03965-14, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa20704
Kelly, S., Kelly, D., Parker, J., & Warrilow, A. (2013). Azole Affinity of Sterol 14alpha-Demethylase (CYP51) Enzymes from Candida albicans and Homo sapiens. Antimicrobial Agents and Chemotherapy, 57(3)-1360.
https://doi.org/10.1128/AAC.02067-12, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa14415
Warrilow, A., Martel, C., Parker, J., Melo, N., Lamb, D., Nes, W., Kelly, D., Kelly, S., & Hull, C. (2010). Azole Binding Properties of Candida albicans Sterol 14alpha-Demethylase (CaCYP51). Antimicrobial Agents and Chemotherapy, 54(10), 4235-4245.
https://doi.org/10.1128/AAC.00587-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6355
Parker, J., Warrilow, A., Price, C., Mullins, J., Kelly, D., & Kelly, S. (2014). Resistance to antifungals that target CYP51. Journal of Chemical Biology, 7(4), 143-161.
https://doi.org/10.1007/s12154-014-0121-1, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa18694
Parker, J., Warrilow, A., Cools, H., Martel, C., Nes, W., Fraaije, B., Lucas, J., Kelly, D., Kelly, S., & Hull, C. (2010). Mechanism of Binding of Prothioconazole to Mycosphaerella graminicola CYP51 Differs from That of Other Azole Antifungals. Applied and Environmental Microbiology, 77(4), 1460-1465.
https://doi.org/10.1128/AEM.01332-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6361
Melo, N., Moran, G., Warrilow, A., Dudley, E., Smith, S., Sullivan, D., Lamb, D., Kelly, D., Coleman, D., & Kelly, S. (2008). CYP56 (Dit2p) in Candida albicans: Characterization and Investigation of Its Role in Growth and Antifungal Drug Susceptibility. Antimicrobial Agents and Chemotherapy, 52(10), 3718-3724.
https://doi.org/10.1128/AAC.00446-08, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6349
Warrilow, A., Ugochukwu, C., Lamb, D., Kelly, D., & Kelly, S. (2008). Expression and Characterization of CYP51, the Ancient Sterol 14alpha-demethylase Activity for Cytochromes P450 (CYP), in the White-Rot Fungus Phanerochaete chrysosporium. Lipids, 43(12), 1143-1153.
https://doi.org/10.1007/s11745-008-3239-5, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6350
Warrilow, A., Jackson, C., Parker, J., Marczylo, T., Kelly, D., Lamb, D., & Kelly, S. (2008). Identification, Characterization, and Azole-Binding Properties of Mycobacterium smegmatis CYP164A2, a Homolog of ML2088, the Sole Cytochrome P450 Gene of Mycobacterium leprae. Antimicrobial Agents and Chemotherapy, 53(3), 1157-1164.
https://doi.org/10.1128/AAC.01237-08, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6351
Lamb, D., Lei, L., Warrilow, A., Lepesheva, G., Mullins, J., Waterman, M., Kelly, S., & Mullins, J. (2009). The First Virally Encoded Cytochrome P450. Journal of Virology, 83(16), 8266-8269.
https://doi.org/10.1128/JVI.00289-09, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6352
Martel, C., Parker, J., Bader, O., Weig, M., Gross, U., Warrilow, A., Kelly, D., Kelly, S., Parker, J., & Hull, C. (2010). A Clinical Isolate of Candida albicans with Mutations in ERG11 (Encoding Sterol 14alpha-Demethylase) and ERG5 (Encoding C22 Desaturase) Is Cross Resistant to Azoles and Amphotericin B. Antimicrobial Agents and Chemotherapy, 54(9), 3578-3583.
https://doi.org/10.1128/AAC.00303-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6353
Warrilow, A., Melo, N., Martel, C., Parker, J., Nes, W., Kelly, S., & Kelly, D. (2010). Expression, Purification, and Characterization of Aspergillus fumigatus Sterol 14alpha-Demethylase (CYP51) Isoenzymes A and B. Antimicrobial Agents and Chemotherapy, 54(10), 4225-4234.
https://doi.org/10.1128/AAC.00316-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6354
Martel, C., Parker, J., Warrilow, A., Rolley, N., Kelly, S., Kelly, D., Parker, J., Hull, C., & Warrilow, A. (2010). Complementation of a Saccharomyces cerevisiae ERG11/CYP51 (Sterol 14alpha-Demethylase) Doxycycline-Regulated Mutant and Screening of the Azole Sensitivity of Aspergillus fumigatus Isoenzymes CYP51A and CYP51B. Antimicrobial Agents and Chemotherapy, 54(11), 4920-4923.
https://doi.org/10.1128/AAC.00349-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6356
Lamb, D., Lei, L., Zhao, B., Yuan, H., Jackson, C., Warrilow, A., Skaug, T., Dyson, P., Dawson, E., Kelly, S., Hachey, D., & Waterman, M. (2010). Streptomyces coelicolor A3(2) CYP102 Protein, a Novel Fatty Acid Hydroxylase Encoded as a Heme Domain without an N-Terminal Redox Partner. Applied and Environmental Microbiology, 76(6), 1975-1980.
https://doi.org/10.1128/AEM.03000-09, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6357
Martel, C., Parker, J., Bader, O., Weig, M., Gross, U., Warrilow, A., Rolley, N., Kelly, D., Kelly, S., & Hull, C. (2010). Identification and Characterization of Four Azole-Resistant erg3 Mutants of Candida albicans. Antimicrobial Agents and Chemotherapy, 54(11), 4527-4533.
https://doi.org/10.1128/AAC.00348-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6358
Martel, C., Warrilow, A., Jackson, C., Mullins, J., Togawa, R., Parker, J., Morris, M., Donnison, I., Kelly, D., Kelly, S., Mullins, J., & Hull, C. (2010). Expression, purification and use of the soluble domain of Lactobacillus paracasei β-fructosidase to optimise production of bioethanol from grass fructans. Bioresource Technology, 101(12), 4395-4402.
https://doi.org/10.1016/j.biortech.2010.01.084, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6359
Martel, C., Parker, J., Jackson, C., Warrilow, A., Rolley, N., Greig, C., Morris, S., Donnison, I., Kelly, D., Kelly, S., & Hull, C. (2011). Expression of bacterial levanase in yeast enables simultaneous saccharification and fermentation of grass juice to bioethanol. Bioresource Technology, 102(2), 1503-1508.
https://doi.org/10.1016/j.biortech.2010.07.099, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6360
Agnew, C., Warrilow, A., Burton, N., Lamb, D., Kelly, S., & Brady, R. (2011). An Enlarged, Adaptable Active Site in CYP164 Family P450 Enzymes, the Sole P450 in Mycobacterium leprae. Antimicrobial Agents and Chemotherapy, 56(1), 391-402.
https://doi.org/10.1128/AAC.05227-11, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6364
Hull, C., Parker, J., Bader, O., Weig, M., Gross, U., Warrilow, A., Kelly, D., & Kelly, S. (2012). Facultative Sterol Uptake in an Ergosterol-Deficient Clinical Isolate of Candida glabrata Harboring a Missense Mutation inERG11and Exhibiting Cross-Resistance to Azoles and Amphotericin B. Antimicrobial Agents and Chemotherapy, 56(8), 4223-4232.
https://doi.org/10.1128/aac.06253-11, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa12338
http://dx.doi.org/10.1128/aac.06253-11
Hull, C., Bader, O., Parker, J., Weig, M., Gross, U., Warrilow, A., Kelly, D., & Kelly, S. (2012). Two Clinical Isolates of Candida glabrata Exhibiting Reduced Sensitivity to Amphotericin B Both Harbor Mutations inERG2. Antimicrobial Agents and Chemotherapy, 56(12), 6417-6421.
https://doi.org/10.1128/aac.01145-12, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa13028
http://dx.doi.org/10.1128/aac.01145-12
Calabrese, E., Castellano, S., Santoriello, M., Sgherri, C., Quartacci, M., Calucci, L., Warrilow, A., Lamb, D., Kelly, S., Milite, C., Granata, I., Sbardella, G., Stefancich, G., Maresca, B., & Porta, A. (2013). Antifungal activity of azole compounds CPA18 and CPA109 against azole-susceptible and -resistant strains of Candida albicans. Journal of Antimicrobial Chemotherapy, 68(5), 1111-1119.
https://doi.org/10.1093/jac/dks506, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa14005
Binjubair, F., Parker, J., Warrilow, A., Puri, K., Braidley, P., Tatar, E., Kelly, S., Kelly, D., & Simons, C. (2020). Small‐Molecule Inhibitors Targeting Sterol 14α‐Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans. ChemMedChem, 15(14), 1294-1309.
https://doi.org/10.1002/cmdc.202000250, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa54878
Price, C., Warrilow, A., Rolley, N., Parker, J., Thoss, V., Kelly, D., Corcionivoschi, N., & Kelly, S. (2022). Cytochrome P450 168A1 from Pseudomonas aeruginosa is involved in the hydroxylation of biologically relevant fatty acids. PLOS ONE, 17(3), e0265227
https://doi.org/10.1371/journal.pone.0265227, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa59697
Hull, C., Warrilow, A., Rolley, N., Price, C., Donnison, I., Kelly, D., & Kelly, S. (2017). Co-production of 11α-hydroxyprogesterone and ethanol using recombinant yeast expressing fungal steroid hydroxylases. Biotechnology for Biofuels, 10(1)
https://doi.org/10.1186/s13068-017-0904-z, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa64804
http://dx.doi.org/10.1186/s13068-017-0904-z

Holl Ymchwil

Erthyglau Cylchgronau

Price, C., Warrilow, A., Rolley, N., Parker, J., Thoss, V., Kelly, D., Corcionivoschi, N., & Kelly, S. (2022). Cytochrome P450 168A1 from Pseudomonas aeruginosa is involved in the hydroxylation of biologically relevant fatty acids. PLOS ONE, 17(3), e0265227
https://doi.org/10.1371/journal.pone.0265227, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa59697
Binjubair, F., Parker, J., Warrilow, A., Puri, K., Braidley, P., Tatar, E., Kelly, S., Kelly, D., & Simons, C. (2020). Small‐Molecule Inhibitors Targeting Sterol 14α‐Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans. ChemMedChem, 15(14), 1294-1309.
https://doi.org/10.1002/cmdc.202000250, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa54878
Warrilow, A., Parker, J., Price, C., Rolley, N., Nes, W., Kelly, D., & Kelly, S. (2019). Isavuconazole and voriconazole inhibition of sterol 14α-demethylases (CYP51) from Aspergillus fumigatus and Homo sapiens. International Journal of Antimicrobial Agents
https://doi.org/10.1016/j.ijantimicag.2019.07.011, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa51096
Lamb, D., Follmer, A., Goldstone, J., Nelson, D., Warrilow, A., Price, C., True, M., Kelly, S., Poulos, T., & Stegeman, J. (2019). On the occurrence of cytochrome P450 in viruses. Proceedings of the National Academy of Sciences, 116(25), 12343-12352.
https://doi.org/10.1073/pnas.1901080116, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa50802
Warrilow, A., Nishimoto, A., Parker, J., Price, C., Flowers, S., Kelly, D., Rogers, P., & Kelly, S. (2019). The Evolution of Azole Resistance in Candida albicans Sterol 14α-Demethylase (CYP51) through Incremental Amino Acid Substitutions. Antimicrobial Agents and Chemotherapy, 63(5)
https://doi.org/10.1128/aac.02586-18, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa48946
Zhou, W., Warrilow, A., Thomas, C., Ramos, E., Parker, J., Price, C., Vanderloop, B., Fisher, P., Loftis, M., Kelly, D., Kelly, S., & Nes, W. (2018). Functional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1863(10), 1164-1178.
https://doi.org/10.1016/j.bbalip.2018.07.004, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa41148
Colley, T., Sehra, G., Chowdhary, A., Alanio, A., Kelly, S., Kizawa, Y., Armstrong-James, D., Fisher, M., Warrilow, A., Parker, J., Kelly, D., Kimura, G., Nishimoto, Y., Sunose, M., Onions, S., Crepin, D., Lagasse, F., Crittall, M., Shannon, J...., & Rapeport, G. (2018). In Vitro and In Vivo Efficacy of a Novel and Long-Acting Fungicidal Azole, PC1244, on Aspergillus fumigatus Infection. Antimicrobial Agents and Chemotherapy, 62(5), AAC.01941-17
https://doi.org/10.1128/aac.01941-17, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa38876
http://dx.doi.org/10.1128/aac.01941-17
Hull, C., Warrilow, A., Rolley, N., Price, C., Donnison, I., Kelly, D., & Kelly, S. (2017). Co-production of 11α-hydroxyprogesterone and ethanol using recombinant yeast expressing fungal steroid hydroxylases. Biotechnology for Biofuels, 10(1)
https://doi.org/10.1186/s13068-017-0904-z, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa64804
http://dx.doi.org/10.1186/s13068-017-0904-z
Hull, C., Warrilow, A., Rolley, N., Price, C., Donnison, I., Kelly, D., & Kelly, S. (2017). Co-production of 11α-hydroxyprogesterone and ethanol using recombinant yeast expressing fungal steroid hydroxylases. Biotechnology for Biofuels, 10(1)
https://doi.org/10.1186/s13068-017-0904-z, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa37567
Warrilow, A., Parker, J., Price, C., Garvey, E., Hoekstra, W., Schotzinger, R., Wiederhold, N., Nes, W., Kelly, D., & Kelly, S. (2017). The Tetrazole VT-1161 Is a Potent Inhibitor of Trichophyton rubrum through Its Inhibition of T. rubrum CYP51. Antimicrobial Agents and Chemotherapy, 61(7), e00333-17
https://doi.org/10.1128/AAC.00333-17, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa34176
Colley, T., Alanio, A., Kelly, S., Sehra, G., Kizawa, Y., Warrilow, A., Parker, J., Kelly, D., Kimura, G., Anderson-Dring, L., Nakaoki, T., Sunose, M., Onions, S., Crepin, D., Lagasse, F., Crittall, M., Shannon, J., Cooke, M., Bretagne, S...., & Rapeport, G. (2017). In vitro and in vivo antifungal profile of a novel and long acting inhaled azole, PC945, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy, AAC.02280-16
https://doi.org/10.1128/AAC.02280-16, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa32189
Warrilow, A., Price, C., Parker, J., Rolley, N., Smyrniotis, C., Hughes, D., Thoss, V., Nes, W., Kelly, D., Holman, T., & Kelly, S. (2016). Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa. Scientific Reports, 6(1)
https://doi.org/10.1038/srep27690, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa34335
Warrilow, A., Parker, J., Price, C., Nes, W., Garvey, E., Hoekstra, W., Schotzinger, R., Kelly, D., & Kelly, S. (2016). The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme. Antimicrobial Agents and Chemotherapy, 60(8), 4530-4538.
https://doi.org/10.1128/AAC.00349-16, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa29154
Price, C., Parker, J., Warrilow, A., Kelly, D., & Kelly, S. (2015). Azole fungicides - understanding resistance mechanisms in agricultural fungal pathogens. Pest Management Science, n/a-n/a.
https://doi.org/10.1002/ps.4029, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa20922
Lamb, D., Warrilow, A., Rolley, N., Parker, J., Nes, W., Smith, S., Kelly, D., & Kelly, S. (2015). Azole Antifungal Agents To Treat the Human Pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through Inhibition of Sterol 14α-Demethylase (CYP51). Antimicrobial Agents and Chemotherapy, 59(8), 4707-4713.
https://doi.org/10.1128/AAC.00476-15, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa31514
http://aac.asm.org/content/59/8/4707.full.pdf+html
Price, C., Warrilow, A., Parker, J., Mullins, J., Nes, W., Kelly, D., Kelly, S., & Schottel, J. (2015). Novel Substrate Specificity and Temperature-Sensitive Activity of Mycosphaerella graminicola CYP51 Supported by the Native NADPH Cytochrome P450 Reductase. Applied and Environmental Microbiology, 81(10), 3379-3386.
https://doi.org/10.1128/AEM.03965-14, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa20704
Warrilow, A., Hull, C., Rolley, N., Parker, J., Nes, W., Smith, S., Kelly, D., & Kelly, S. (2014). Clotrimazole as a Potent Agent for Treating the Oomycete Fish Pathogen Saprolegnia parasitica through Inhibition of Sterol 14 -Demethylase (CYP51). Applied and Environmental Microbiology, 80(19), 6154-6166.
https://doi.org/10.1128/AEM.01195-14, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa18616
Parker, J., Warrilow, A., Price, C., Mullins, J., Kelly, D., & Kelly, S. (2014). Resistance to antifungals that target CYP51. Journal of Chemical Biology, 7(4), 143-161.
https://doi.org/10.1007/s12154-014-0121-1, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa18694
Warrilow, A., Hull, C., Parker, J., Garvey, E., Hoekstra, W., Moore, W., Schotzinger, R., Kelly, D., Kelly, S., & Hull, C. (2014). 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, 58(12), 7121-7127.
https://doi.org/10.1128/AAC.03707-14, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa18693
Nie, D., Hoobler, E., Rai, G., Warrilow, A., Perry, S., Smyrniotis, C., Jadhav, A., Simeonov, A., Parker, J., Kelly, D., Maloney, D., Kelly, S., & Holman, T. (2013). Discovery of a Novel Dual Fungal CYP51/Human 5-Lipoxygenase Inhibitor: Implications for Anti-Fungal Therapy. PLoS ONE, 8(6)
https://doi.org/10.1371/journal.pone.0065928, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa15178
Calabrese, E., Castellano, S., Santoriello, M., Sgherri, C., Quartacci, M., Calucci, L., Warrilow, A., Lamb, D., Kelly, S., Milite, C., Granata, I., Sbardella, G., Stefancich, G., Maresca, B., & Porta, A. (2013). Antifungal activity of azole compounds CPA18 and CPA109 against azole-susceptible and -resistant strains of Candida albicans. Journal of Antimicrobial Chemotherapy, 68(5), 1111-1119.
https://doi.org/10.1093/jac/dks506, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa14005
Kelly, S., Kelly, D., Parker, J., & Warrilow, A. (2013). Azole Affinity of Sterol 14alpha-Demethylase (CYP51) Enzymes from Candida albicans and Homo sapiens. Antimicrobial Agents and Chemotherapy, 57(3)-1360.
https://doi.org/10.1128/AAC.02067-12, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa14415
Hull, C., Bader, O., Parker, J., Weig, M., Gross, U., Warrilow, A., Kelly, D., & Kelly, S. (2012). Two Clinical Isolates of Candida glabrata Exhibiting Reduced Sensitivity to Amphotericin B Both Harbor Mutations inERG2. Antimicrobial Agents and Chemotherapy, 56(12), 6417-6421.
https://doi.org/10.1128/aac.01145-12, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa13028
http://dx.doi.org/10.1128/aac.01145-12
Hull, C., Parker, J., Bader, O., Weig, M., Gross, U., Warrilow, A., Kelly, D., & Kelly, S. (2012). Facultative Sterol Uptake in an Ergosterol-Deficient Clinical Isolate of Candida glabrata Harboring a Missense Mutation inERG11and Exhibiting Cross-Resistance to Azoles and Amphotericin B. Antimicrobial Agents and Chemotherapy, 56(8), 4223-4232.
https://doi.org/10.1128/aac.06253-11, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa12338
http://dx.doi.org/10.1128/aac.06253-11
Agnew, C., Warrilow, A., Burton, N., Lamb, D., Kelly, S., & Brady, R. (2011). An Enlarged, Adaptable Active Site in CYP164 Family P450 Enzymes, the Sole P450 in Mycobacterium leprae. Antimicrobial Agents and Chemotherapy, 56(1), 391-402.
https://doi.org/10.1128/AAC.05227-11, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6364
Martel, C., Parker, J., Jackson, C., Warrilow, A., Rolley, N., Greig, C., Morris, S., Donnison, I., Kelly, D., Kelly, S., & Hull, C. (2011). Expression of bacterial levanase in yeast enables simultaneous saccharification and fermentation of grass juice to bioethanol. Bioresource Technology, 102(2), 1503-1508.
https://doi.org/10.1016/j.biortech.2010.07.099, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6360
Warrilow, A., Martel, C., Parker, J., Melo, N., Lamb, D., Nes, W., Kelly, D., Kelly, S., & Hull, C. (2010). Azole Binding Properties of Candida albicans Sterol 14alpha-Demethylase (CaCYP51). Antimicrobial Agents and Chemotherapy, 54(10), 4235-4245.
https://doi.org/10.1128/AAC.00587-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6355
Parker, J., Warrilow, A., Cools, H., Martel, C., Nes, W., Fraaije, B., Lucas, J., Kelly, D., Kelly, S., & Hull, C. (2010). Mechanism of Binding of Prothioconazole to Mycosphaerella graminicola CYP51 Differs from That of Other Azole Antifungals. Applied and Environmental Microbiology, 77(4), 1460-1465.
https://doi.org/10.1128/AEM.01332-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6361
Martel, C., Parker, J., Bader, O., Weig, M., Gross, U., Warrilow, A., Kelly, D., Kelly, S., Parker, J., & Hull, C. (2010). A Clinical Isolate of Candida albicans with Mutations in ERG11 (Encoding Sterol 14alpha-Demethylase) and ERG5 (Encoding C22 Desaturase) Is Cross Resistant to Azoles and Amphotericin B. Antimicrobial Agents and Chemotherapy, 54(9), 3578-3583.
https://doi.org/10.1128/AAC.00303-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6353
Warrilow, A., Melo, N., Martel, C., Parker, J., Nes, W., Kelly, S., & Kelly, D. (2010). Expression, Purification, and Characterization of Aspergillus fumigatus Sterol 14alpha-Demethylase (CYP51) Isoenzymes A and B. Antimicrobial Agents and Chemotherapy, 54(10), 4225-4234.
https://doi.org/10.1128/AAC.00316-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6354
Martel, C., Parker, J., Warrilow, A., Rolley, N., Kelly, S., Kelly, D., Parker, J., Hull, C., & Warrilow, A. (2010). Complementation of a Saccharomyces cerevisiae ERG11/CYP51 (Sterol 14alpha-Demethylase) Doxycycline-Regulated Mutant and Screening of the Azole Sensitivity of Aspergillus fumigatus Isoenzymes CYP51A and CYP51B. Antimicrobial Agents and Chemotherapy, 54(11), 4920-4923.
https://doi.org/10.1128/AAC.00349-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6356
Lamb, D., Lei, L., Zhao, B., Yuan, H., Jackson, C., Warrilow, A., Skaug, T., Dyson, P., Dawson, E., Kelly, S., Hachey, D., & Waterman, M. (2010). Streptomyces coelicolor A3(2) CYP102 Protein, a Novel Fatty Acid Hydroxylase Encoded as a Heme Domain without an N-Terminal Redox Partner. Applied and Environmental Microbiology, 76(6), 1975-1980.
https://doi.org/10.1128/AEM.03000-09, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6357
Martel, C., Warrilow, A., Jackson, C., Mullins, J., Togawa, R., Parker, J., Morris, M., Donnison, I., Kelly, D., Kelly, S., Mullins, J., & Hull, C. (2010). Expression, purification and use of the soluble domain of Lactobacillus paracasei β-fructosidase to optimise production of bioethanol from grass fructans. Bioresource Technology, 101(12), 4395-4402.
https://doi.org/10.1016/j.biortech.2010.01.084, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6359
Martel, C., Parker, J., Bader, O., Weig, M., Gross, U., Warrilow, A., Rolley, N., Kelly, D., Kelly, S., & Hull, C. (2010). Identification and Characterization of Four Azole-Resistant erg3 Mutants of Candida albicans. Antimicrobial Agents and Chemotherapy, 54(11), 4527-4533.
https://doi.org/10.1128/AAC.00348-10, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6358
Lamb, D., Lei, L., Warrilow, A., Lepesheva, G., Mullins, J., Waterman, M., Kelly, S., & Mullins, J. (2009). The First Virally Encoded Cytochrome P450. Journal of Virology, 83(16), 8266-8269.
https://doi.org/10.1128/JVI.00289-09, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6352
Melo, N., Moran, G., Warrilow, A., Dudley, E., Smith, S., Sullivan, D., Lamb, D., Kelly, D., Coleman, D., & Kelly, S. (2008). CYP56 (Dit2p) in Candida albicans: Characterization and Investigation of Its Role in Growth and Antifungal Drug Susceptibility. Antimicrobial Agents and Chemotherapy, 52(10), 3718-3724.
https://doi.org/10.1128/AAC.00446-08, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6349
Warrilow, A., Ugochukwu, C., Lamb, D., Kelly, D., & Kelly, S. (2008). Expression and Characterization of CYP51, the Ancient Sterol 14alpha-demethylase Activity for Cytochromes P450 (CYP), in the White-Rot Fungus Phanerochaete chrysosporium. Lipids, 43(12), 1143-1153.
https://doi.org/10.1007/s11745-008-3239-5, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6350
Warrilow, A., Jackson, C., Parker, J., Marczylo, T., Kelly, D., Lamb, D., & Kelly, S. (2008). Identification, Characterization, and Azole-Binding Properties of Mycobacterium smegmatis CYP164A2, a Homolog of ML2088, the Sole Cytochrome P450 Gene of Mycobacterium leprae. Antimicrobial Agents and Chemotherapy, 53(3), 1157-1164.
https://doi.org/10.1128/AAC.01237-08, SU Repository: https://cronfa.swan.ac.uk/Record/cronfa6351

Hanes Gyrfa

Swyddog Ymchwil Ôl-ddoethurol , Ysgol Feddygaeth Prifysgol Abertawe

2004 - Presennol
Cynorthwyydd Ymchwil Ôl-ddoethurol , Labordy Bioamrywiaeth Cytocrom P450 Wolfson, Prifysgol Aberystwyth

1998 - 2004
Uwch Swyddog Gwyddonol, IACR Long Ashton Research Station, Bryste

1995 - 1998
SERC funded PhD studentship - Protein Biochemistry , Adran Biocemeg, Prifysgol Aberystwyth

1989 - 1993

Dr Andrew Warrilow

Rhif ffôn

Cyfeiriad ebost

Trosolwg

Meysydd Arbenigedd

Uchafbwyntiau Gyrfa

Cyhoeddiadau

Uchafbwyntiau Ymchwil

Holl Ymchwil

Erthyglau Cylchgronau

Hanes Gyrfa

Swyddog Ymchwil Ôl-ddoethurol , Ysgol Feddygaeth Prifysgol Abertawe

Cynorthwyydd Ymchwil Ôl-ddoethurol , Labordy Bioamrywiaeth Cytocrom P450 Wolfson, Prifysgol Aberystwyth

Uwch Swyddog Gwyddonol, IACR Long Ashton Research Station, Bryste

SERC funded PhD studentship - Protein Biochemistry , Adran Biocemeg, Prifysgol Aberystwyth