The self-sufficient P450 RhF expressed in a whole cell system selectively catalyses the 5-hydroxylation of diclofenac

Biotechnology Journal

Volumn 12, Issue 3, 2017, Pages

  Klenk, Jan M ^b   Nebel, Bernd A ^b   Porter, Joanne L ^a   Kulig, Justyna K ^c,d   Hussain, Shaneela A ^a   Richter, Sven M ^b   Tavanti, Michele ^a   Turner, Nicholas J ^a   Hayes, Martin A ^c   Hauer, Bernhard ^b   Flitsch, Sabine L ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b UNIVERSITY OF STUTTGART   (Germany)

^c ASTRAZENECA R AND D   (Sweden)

^d BAYER AG   (Germany)

Author keywords

Biocatalysis; Cytochrome P450; Diclofenac; Drug metabolism; Fermentation; Regioselectivity

Indexed keywords

BIOMOLECULES; BORON COMPOUNDS; CATALYSIS; ENZYMES; FERMENTATION; FLUORINE COMPOUNDS; METABOLITES; OXIDATION; REGIOSELECTIVITY; RHODIUM COMPOUNDS; YTTRIUM COMPOUNDS;

ANTI-INFLAMMATORY DRUGS; BIOCATALYSIS; CYTOCHROME P450; DICLOFENAC; DRUG METABOLISMS; REGIOSELECTIVE OXIDATION; STEREOSELECTIVE OXIDATIONS; WHOLE-CELL BIOCATALYSIS;

PHOSPHORUS COMPOUNDS;

5 HYDROXYDICLOFENAC; CYTOCHROME P450; CYTOCHROME P450 RHF; DICLOFENAC; DICLOFENAC DERIVATIVE; DRUG METABOLITE; QUINONE DERIVATIVE; UNCLASSIFIED DRUG; 5-HYDROXYDICLOFENAC; BACTERIAL PROTEIN; NONSTEROID ANTIINFLAMMATORY AGENT;

ARTICLE; AUTOOXIDATION; BIOCATALYSIS; DRUG HYDROXYLATION; DRUG ISOLATION; DRUG OXIDATION; FERMENTATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NONHUMAN; OXIDATION; PRIORITY JOURNAL; PROCESS OPTIMIZATION; RHODOCOCCUS; SCALE UP; WHOLE CELL; ANALOGS AND DERIVATIVES; BIOREMEDIATION; BIOTRANSFORMATION; CATALYSIS; CHEMISTRY; ENZYMOLOGY; GENETICS; HYDROXYLATION; METABOLISM; OXIDATION REDUCTION REACTION;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BACTERIAL PROTEINS; BIODEGRADATION, ENVIRONMENTAL; BIOTRANSFORMATION; CATALYSIS; CYTOCHROME P-450 ENZYME SYSTEM; DICLOFENAC; FERMENTATION; HYDROXYLATION; OXIDATION-REDUCTION; QUINONES; RHODOCOCCUS;

EID: 85012885755     PISSN: 18606768     EISSN: 18607314     Source Type: Journal    
DOI: 10.1002/biot.201600520     Document Type: Article

References (40)

1. Langford, K., Thomas, K. V., Input of selected human pharmaceutical metabolites into the Norwegian aquatic environment. J. Environ. Monit. 2011, 13, 416–421.
2. Richardson, S. D., Ternes, T. A., Water analysis: Emerging contaminants and current issues. Anal. Chem. 2014, 86, 2813–2848.
3. Martin, J., Camacho-Munoz, D., Santos, J. L., Aparicio, I., Alonso, E., Occurrence of pharmaceutical compounds in wastewater and sludge from wastewater treatment plants: Removal and ecotoxicological impact of wastewater discharges and sludge disposal. J. Hazard. Mater. 2012, 239–240, 40–47.
4. Guengerich, F. P., Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J. 2006, 8, E101-E111.
5. Zhang, K., Shafer, B. M., Demars, M. D., Stern, H. A., Fasan, R., Controlled oxidation of remote sp3 C-H bonds in artemisinin via P450 catalysts with fine-tuned regio- and stereoselectivity. J. Am. Chem. Soc. 2012, 134, 18695–18704.
6. Osorio, V., Imbert-Bouchard, M., Zonja, B., Abad, J.-L. et al., Simultaneous determination of diclofenac, its human metabolites and microbial nitration/nitrosation transformation products in wastewaters by liquid chromatography/quadrupole-linear ion trap mass spectrometry. J. Chromatogr. A 2014, 1347, 63–71.
7. Scheurell, M., Franke, S., Shah, R. M., Huehnerfuss, H., Occurrence of diclofenac and its metabolites in surface water and effluent samples from Karachi, Pakistan. Chemosphere 2009, 77, 870–876.
8. Landwehr, M., Hochrein, L., Otey, C. R., Kasrayan, A. et al., Enantioselective α-hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3. J. Am. Chem. Soc. 2006, 128, 6058–6059.
9. Kille, S., Zilly, F. E., Acevedo, J. P., Reetz, M. T., Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids controlled by laboratory evolution. Nat. Chem. 2011, 3, 738–743.
10. Munro, A. W., Leys, D. G., McLean, K. J., Marshall, K. R. et al., P450 BM3: the very model of a modern flavocytochrome. Trends Biochem. Sci 2002, 27, 250–257.
11. Tsotsou, G. E., Sideri, A., Goyal, A., Di Nardo, G., Gilardi, G., Identification of mutant Asp251Gly/Gln307His of cytochrome P450 BM3 for the generation of metabolites of diclofenac, ibuprofen and tolbutamide. Chem. Eur. J. 2012, 18, 3582–3588.
12. Di Nardo, G., Dell'Angelo, V., Catucci, G., Sadeghi, S. J., Gilardi, G., Subtle structural changes in the Asp251Gly/Gln307His P450 BM3 mutant responsible for new activity toward diclofenac, tolbutamide and ibuprofen. Arch. Biochem. Biophys. 2016, 602, 106–115.
13. Ren, X., Yorke, J. A., Taylor, E., Zhang, T. et al., Drug oxidation by cytochrome P450 BM3: metabolite synthesis and discovering new P450 reaction types. Chem. Eur. J. 2015, 21, 15039–15047.
14. Naisbitt, D. J., Sanderson, L. S., Meng, X., Stachulski, A. V. et al., Investigation of the immunogenicity of diclofenac and diclofenac metabolites. Toxicol. Lett. 2007, 168, 45–50.
15. Kenny, J. R., Maggs, J. L., Meng, X., Sinnott, D. et al., Syntheses and characterization of the acyl glucuronide and hydroxy metabolites of diclofenac. J. Med. Chem. 2004, 47, 2816–2825.
16. O'Reilly, E., Kohler, V., Flitsch, S. L., Turner, N. J., Cytochromes P450 as useful biocatalysts: Addressing the limitations. Chem. Commun. 2011, 47, 2490–2501.
17. Lundemo, M. T., Woodley, J. M., Guidelines for development and implementation of biocatalytic P450 processes. Appl. Microbiol. Biotechnol. 2015, 99, 2465–2483.
18. Bernhardt, R., Urlacher, V. B., Cytochromes P450 as promising catalysts for biotechnological application: chances and limitations. Appl. Microbiol. Biotechnol. 2014, 98, 6185–6203.
19. Schewe, H., Holtmann, D., Schrader, J., P450BM-3-catalyzed whole-cell biotransformation of α-pinene with recombinant Escherichia coli in an aqueous–organic two-phase system. Appl. Microbiol. Biotechnol. 2009, 83, 849–857.
20. Vail, R. B., Homann, M. J., Hanna, I., Zaks, A., Preparative synthesis of drug metabolites using human cytochrome P450s 3A4, 2C9 and 1A2 with NADPH-P450 reductase expressed in Escherichia coli. J. Ind. Microbiol. Biotechnol. 2005, 32, 67–74.
21. Caswell, J. M., O'Neill, M., Taylor, S. J., Moody, T. S., Engineering and application of P450 monooxygenases in pharmaceutical and metabolite synthesis. Curr. Opin. Chem. Biol. 2013, 17, 271–275.
22. Sawayama, A. M., Chen, M. M., Kulanthaivel, P., Kuo, M. S. et al., A panel of cytochrome P450 BM3 variants to produce drug metabolites and diversify lead compounds. Chemistry 2009, 15, 11723–11729.
23. Kaluzna, I., Schmitges, T., Straatman, H., van Tegelen, D. et al., Enabling selective and sustainable P450 oxygenation technology. Production of 4-hydroxy-α-isophorone on kilogram scale. Org. Process Res. Dev. 2016, 20, 814–819.
24. Brummund, J., Muller, M., Schmitges, T., Kaluzna, I. et al., Process development for oxidations of hydrophobic compounds applying cytochrome P450 monooxygenases in-vitro. J. Biotechnol. 2016, 233, 143–150.
25. Dragan, C. A., Peters, F. T., Bour, P., Schwaninger, A. E. et al., Convenient gram-scale metabolite synthesis by engineered fission yeast strains expressing functional human P450 systems. Appl. Biochem. Biotechnol. 2011, 163, 965–980.
26. Paddon, C. J., Westfall, P. J., Pitera, D. J., Benjamin, K. et al., High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 2013, 496, 528–532.
27. O'Reilly, E., Corbett, M., Hussain, S., Kelly, P. P. et al., Substrate promiscuity of cytochrome P450 RhF. Catal. Sci. Technol. 2013, 3, 1490–1492.
28. Omura, T., Sato, R., The carbon monoxide-binding pigment of liver microsomes: I. evidence for its hemoprotein nature. J. Biol. Chem. 1964, 239, 2370–2378.
29. Hunter, D. J. B., Roberts, G. A., Ost, T. W. B., White, J. H. et al., Analysis of the domain properties of the novel cytochrome P450 RhF. FEBS Lett. 2005, 579, 2215–2220.
30. Roberts, G. A., Celik, A., Hunter, D. J. B., Ost, T. W. B. et al., A self-sufficient cytochrome P450 with a primary structural organization that includes a flavin domain and a [2Fe-2S] redox center. J. Biol. Chem. 2003, 278, 48914–48920.
31. Sabbadin, F., Hyde, R., Robin, A., Hilgarth, E.-M., et al., LICRED: A versatile drop-in vector for rapid generation of redox-self-sufficient cytochrome P450s. ChemBioChem 2010, 11, 987–994.
32. Marisch, K., Bayer, K., Cserjan-Puschmann, M., Luchner, M., Striedner, G., Evaluation of three industrial Escherichia coli strains in fed-batch cultivations during high-level SOD protein production. Microb. Cell. Fact. 2013, 12.
33. Pflug, S., Richter, S. M., Urlacher, V. B., Development of a fed-batch process for the production of the cytochrome P450 monooxygenase CYP102A1 from Bacillus megaterium in E. coli. J. Biotechnol. 2007, 129, 481–488.
34. Khatri, Y., Hannemann, F., Ewen, K. M., Pistorius, D. et al., The CYPome of Sorangium cellulosum So ce56 and identification of CYP109D1 as a new fatty acid hydroxylase. Chem. Biol. 2010, 17, 1295–1305.
35. Hoffmann, S. M., Weissenborn, M. J., Gricman, Ł., Notonier, S. et al., The impact of linker length on P450 fusion constructs: Activity, stability and coupling. ChemCatChem 2016, 8, 1591–1597.
36. Walton, A. Z., Stewart, J. D., Understanding and improving NADPH-dependent reactions by nongrowing Escherichia coli cells. Biotechnol. Progr. 2004, 20, 403–411.
37. Fuhrer, T., Sauer, U., Different biochemical mechanisms ensure network-wide balancing of reducing equivalents in microbial metabolism. J. Bacteriol. 2009, 191, 2112–2121.
38. Sauer, U., Canonaco, F., Heri, S., Perrenoud, A., Fischer, E., The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli. J. Biol. Chem. 2004, 279, 6613–6619.
39. Shen, S., Marchick, M. R., Davis, M. R., Doss, G. A., Pohl, L. R., Metabolic activation of diclofenac by human cytochrome P450 3A4: Role of 5-hydroxydiclofenac. Chem. Res. Toxicol. 1999, 12, 214–222.
40. den Braver, M. W., den Braver-Sewradj, S. P., Vermeulen, N. P. E., Commandeur, J. N. M., Characterization of cytochrome P450 isoforms involved in sequential two-step bioactivation of diclofenac to reactive p-benzoquinone imines. Toxicol. Lett. 2016, 253, 46–54.