Abstract
Fluoxetine (FLX) is a blockbuster drug with annual sales in the billions of dollars. Its widespread use has resulted in its detection in water courses, where it impacts aquatic life. Investigations on the biodegradation of FLX by microorganisms are important, since augmentation of secondary wastewater treatment by an effective degrader may be one method of improving the drug’s removal. In this paper, we demonstrate that common environmental bacteria can use FLX as a sole carbon and energy source. Investigations into the metabolites formed using fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR) and gas chromatography–mass spectrometry indicated that the drug was initially hydrolysed to yield 4-(trifluoromethyl)phenol (TFMP) and 3-(methylamino)-1-phenylpropan-1-ol. Since the fluorometabolite accumulated, the bacteria presumably used the latter compound for carbon and energy. Further growth studies revealed that TFMP could also be used as a sole carbon and energy source and was most likely catabolised via meta-cleavage, since semialdehyde products were detected in culture supernatants. The final products of the degradation pathway were trifluoroacetate and fluoride ion; the former is a dead-end product and was not further catabolised. Fluoride ion most likely arises owing to spontaneous defluorination of the meta-cleavage products that were shown to be photolabile.
Key points
• Bacteria can use FLX and TFMP as sole carbon and energy sources for their growth.
• Biodegradation produces fluorometabolites that were detected by 19F NMR and GC–MS.
• Trifluoroacetic acid and fluoride ion were identified as end products.
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References
Alexandrino DAM, Ribeiro I, Pinto LM, Cambra R, Oliveira RS, Pereira F, Carvalho MF (2018) Biodegradation of mono-, di- and trifluoroacetate by microbial cultures with different origins. New Biotechnol 43:23–29. https://doi.org/10.1016/j.nbt.2017.08.005
Amorim CL, Carvalho MF, Afonso CMM, Castro PML (2013) Biodegradation of fluoroanilines by the wild strain Labrys portucalensis. Int Biodeterior Biodegradation 80:10–15. https://doi.org/10.1016/j.ibiod.2013.02.001
Benfield P, Heel RC, Lewis SP (1986) Fluoxetine - a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive-illness. Drugs 32(6):481–508. https://doi.org/10.2165/00003495-198632060-00002
Brooks BW, Turner PK, Stanley JK, Weston JJ, Glidewell EA, Foran CM, Slattery M, La Point TW, Huggett DB (2003) Waterborne and sediment toxicity of fluoxetine to select organisms. Chemosphere 52(1):135–142. https://doi.org/10.1016/s0045-6535(03)00103-6
Carvalho MF, Jorge RF, Pacheco CC, De Marco P, Castro PML (2005) Isolation and properties of a pure bacterial strain capable of fluorobenzene degradation as sole carbon and energy source. Environ Microbiol 7(2):294–298. https://doi.org/10.1111/j.1462-2920.2004.00714.x
Chi BK, Kobayashi K, Albrecht D, Hecker M, Antelmann H (2010) The paralogous MarR/DUF24-family repressors yodb and catr control expression of the catechol dioxygenase CatE in Bacillus subtilis. J Bacteriol 192(18):4571–4581. https://doi.org/10.1128/jb.00409-10
de la Torre BG, Albericio F (2021) The Pharmaceutical Industry in 2020. An analysis of FDA drug approvals from the perspective of molecules. Molecules 26(3) https://doi.org/10.3390/molecules26030627
Deere JR, Streets S, Jankowski MD, Ferrey M, Chenaux-Ibrahim Y, Convertino M, Isaac EJ, Phelps NBD, Primus A, Servadio JL, Singer RS, Travis DA, Seth M, Wolf TM (2021) A chemical prioritization process: applications to contaminants of emerging concern in freshwater ecosystems (Phase I). Sci Total Environ 772. https://doi.org/10.1016/j.scitotenv.2021.146030
Donnelly C, Murphy CD (2007) Bacterial defluorination of 4-fluoroglutamic acid. Appl Microbiol Biotechnol 77(3):699–703. https://doi.org/10.1007/s00253-007-1200-9
Engesser KH, Rubio MA, Ribbons DW (1988) Bacterial metabolism of side-chain fluorinated aromatics - co-metabolism of 4-trifluoromethyl(tfm)-benzoate by 4-isopropylbenzoate grown Pseudomonas putida JY strains. Arch Microbiol 149(3):198–206. https://doi.org/10.1007/bf00422005
Han JL, Remete AM, Dobson LS, Kiss L, Izawa K, Moriwaki H, Soloshonok VA, O'Hagan D (2020) Next generation organofluorine containing blockbuster drugs. J Fluor Chem 239. https://doi.org/10.1016/j.jfluchem.2020.109639
Khan MF, Murphy CD (2021) Cunninghamella spp. produce mammalian-equivalent metabolites from fluorinated pyrethroid pesticides. AMB Express 11(1) https://doi.org/10.1186/s13568-021-01262-0
Kiel M, Engesser KH (2015) The biodegradation vs. biotransformation of fluorosubstituted aromatics. Appl Microbiol Biotechnol 99(18):7433–7464. https://doi.org/10.1007/s00253-015-6817-5
Kwon JW, Armbrust KL (2006) Laboratory persistence and fate of fluoxetine in aquatic environments. Environ Toxicol Chem 25(10):2561–2568. https://doi.org/10.1897/05-613r.1
Ma RX, Qu H, Wang B, Wang F, Yu G (2020) Widespread monitoring of chiral pharmaceuticals in urban rivers reveals stereospecific occurrence and transformation. Environ Int 138. https://doi.org/10.1016/j.envint.2020.105657
Moreira IS, Ribeiro AR, Afonso CM, Tiritan ME, Castro PML (2014) Enantioselective biodegradation of fluoxetine by the bacterial strain Labrys portucalensis F11. Chemosphere 111:103–111. https://doi.org/10.1016/j.chemosphere.2014.03.022
Murphy CD (2016) Microbial degradation of fluorinated drugs: biochemical pathways, impacts on the environment and potential applications. Appl Microbiol Biotechnol 100(6):2617–2627. https://doi.org/10.1007/s00253-016-7304-3
Nakanishi Y, Murakami S, Shinke R, Aoki K (1991) Induction, purification, and characterization of catechol 2,3-dioxygenase from aniline-assimilating Pseudomonas sp. FK-8–2. Agric Biol Chem 55(5):1281–1289. https://doi.org/10.1080/00021369.1991.10870759
Palma TL, Shylova A, Carlier JD, Costa MC (2021) An autochthonous aerobic bacterial community and its cultivable isolates capable of degrading fluoxetine. J Chem Technol Biotechnol. https://doi.org/10.1002/jctb.6829
Reinscheid UM, Zuilhof H, Muller R, Vervoort J (1998) Biological, thermal and photochemical transformation of 2-trifluoromethylphenol. Biodegradation 9(6):487–499. https://doi.org/10.1023/a:1008394115008
Shi W, Han Y, Guan XF, Rong JH, Su WH, Zha SJ, Tang Y, Du XY, Liu GX (2019) Fluoxetine suppresses the immune responses of blood clams by reducing haemocyte viability, disturbing signal transduction and imposing physiological stress. Sci Total Environ 683:681–689. https://doi.org/10.1016/j.scitotenv.2019.05.308
Srain HS, Beazley KF, Walker TR (2021) Pharmaceuticals and personal care products and their sublethal and lethal effects in aquatic organisms. Environ Rev 29(2):142–181. https://doi.org/10.1139/er-2020-0054
Sun M, Cui JN, Guo JY, Zhai ZH, Zuo P, Zhang JB (2020) Fluorochemicals biodegradation as a potential source of trifluoroacetic acid (TFA) to the environment. Chemosphere 254. https://doi.org/10.1016/j.chemosphere.2020.126894
Taylor BF, Amador JA, Levinson HS (1993) Degradation of meta-trifluoromethylbenzoate by sequential microbial and photochemical treatments. FEMS Microbiol Lett 110(2):213–216. https://doi.org/10.1016/0378-1097(93)90468-h
Tong W, Huang Q, Li M, Wang JB (2019) Enzyme-catalyzed C-F bond formation and cleavage. Bioresources and Bioprocessing 6(1) https://doi.org/10.1186/s40643-019-0280-6
Velazquez YF, Nacheva PM (2017) Biodegradability of fluoxetine, mefenamic acid, and metoprolol using different microbial consortiums. Environ Sci Pollut Res 24(7):6779–6793. https://doi.org/10.1007/s11356-017-8413-y
Yano K, Wachi M, Tsuchida S, Kitazume T, Iwai N (2015) Degradation of benzotrifluoride via the dioxygenase pathway in Rhodococcus sp. 065240. Biosci Biotechnol Biochem 79(3):496–504. https://doi.org/10.1080/09168451.2014.982502
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This study was funded by a Government of Ireland Postdoctoral Fellowship from the Irish Research Council (IRC/GOI-PD/1064).
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MFK and CDM conceived and designed the research. MFK conducted the experiments and analysed the data. CDM wrote the manuscript. Both authors read and approved the manuscript.
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Khan, M.F., Murphy, C.D. Bacterial degradation of the anti-depressant drug fluoxetine produces trifluoroacetic acid and fluoride ion. Appl Microbiol Biotechnol 105, 9359–9369 (2021). https://doi.org/10.1007/s00253-021-11675-3
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DOI: https://doi.org/10.1007/s00253-021-11675-3