Metabolism of Furanocoumarins by Three Recombinant CYP9A Proteins From the Polyphagous Cotton Bollworm Helicoverpa armigera.

Furanocoumarins are a class of chemical compounds with phototoxic properties. For herbivores, efficient detoxification of such defense compounds is the prerequisite to feed successfully on furanocoumarin-containing plants. The cotton bollworm Helicoverpa armigera is a very important polyphagous pest in agriculture, but how it copes with toxic furanocoumarins in some of its host plants is not well understood. Given that cytochrome P450s are well known for their capacity in xenobiotic metabolism, this study attempted to explore the potential roles of cytochrome P450s in furanocoumarin transformation in this pest. Our data showed that two linear structures (psoralen and xanthotoxin) could be metabolized by three recombinant CYP9A enzymes, but no detectable depletion was observed for the linear one with the 8-dimethylallyloxy substituent on the coumarin moiety (imperatorin) and the angular furanocoumarin (angelicin). Initial epoxidation of the double bond connecting C2' and C3' of the furano ring following by cleavage of the epoxidated furan ring, leading to the formation of more soluble, less reactive and nonphotosensitizing metabolites, was identified as a common mechanism of linear furanocoumarin metabolism using a quadrupole/time-of-flight (Q-TOF) mass spectrometry interfaced with a high performance liquid chromatography (HPLC) system. Our data demonstrated that multiple P450s were involved in the detoxification of linear furanocoumarins in the cotton bollworm. These findings contribute to a better understanding of the biochemical basis of adaptation to plant defense chemicals in this economically important pest.