Cunninghamella spp. produce mammalian-equivalent metabolites from fluorinated pyrethroid pesticides

Abstract

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.

Keywords

• Biotransformation
• cytochrome P450
• 19F NMR
• fungi
• insecticide