Abstract
Cunninghamella spp. are fungi that are routinely used to model the metabolism of drugs. In this paper we demonstrate that they can be employed to generate mammalian-equivalent metabolites of the pyrethroid pesticides transfluthrin and β-cyfluthrin, both of which are fluorinated. The pesticides were incubated with grown cultures of Cunninghamella elegans, C. blakesleeana and C. echinulata and the biotransformation monitored using fluorine-19 nuclear magnetic resonance spectroscopy. Transfluthrin was initially absorbed in the biomass, but after 72 h a new fluorometabolite appeared in the supernatant; although all three species yielded this compound, it was most prominent in C. blakesleeana. In contrast β-cyfluthrin mostly remained in the fungal biomasss and only minor biotransformation was observed. Gas chromatography-mass spectrometry (GC–MS) analysis of culture supernatant extracts revealed the identity of the fluorinated metabolite of transfluthrin to be tetrafluorobenzyl alcohol, which arose from the cytochrome P450-catalysed cleavage of the ester bond in the pesticide. The other product of this hydrolysis, dichlorovinyl-2,2-dimethylcyclopropane carboxylic acid, was also detected by GC–MS and was a product of β-cyfluthrin metabolism too. Upon incubation with rat liver microsomes the same products were detected, demonstrating that the fungi can be used as models of mammalian metabolism of fluorinated pesticides.
Highlights
In contrast to the very small number of fluorinated natural products that are known, approximately 30% of agrochemicals contain fluorine (Ogawa et al 2020)
The biotransformation of the pyrethroids was monitored over time using 19 nuclear magnetic resonance (19F NMR) in the first instance, after the cultures had been extracted with ethyl acetate
We investigated the biotransformation of two fluorinated pyrethroids transfluthrin and β-cyfluthrin in three species belonging to the fungal genus Cunninghamella
Summary
In contrast to the very small number of fluorinated natural products that are known, approximately 30% of agrochemicals contain fluorine (Ogawa et al 2020). Fluorine’s attractiveness lies in its unusual properties of small atomic size, high electronegativity, high redox potential and strength of the carbon-fluorine bond. Bioactive compounds that contain fluorine have enhanced characteristics in terms of metabolic stability, lipophilicity and enzyme/receptor binding. The increasing application of fluorinated compounds in agriculture, amongst other industries, has resulted in environmental pollution with these xenobiotics and their metabolic by-products (Murphy and Sandford 2015). The stability of the C-F bond, which is an advantage in certain circumstances, often means that complete biodegradation is not possible. Organisms are exposed to these xenobiotics, or
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