Decreased sensitivity of mixed-function oxidases from papilio polyxenes to inhibitors in host plants

Caterpillars of Papilio polyxenes, the black swallowtail, feed on umbellifers that contain both toxic furanocoumarins and methylenedioxyphenyl compounds such as myristicin and safrole. These phytosynergists enhance the toxicity of furanocoumarins by inhibiting mixed-function oxidases (MFOs), the detoxification enzymes responsible for metabolizing furanocoumarins. In model substrate assays, MFOs from P. polyxenes are twice as active as MFOs from Heliothis zea, a generalist herbivore not adapted to feeding on either furanocoumarins or furanocoumarin/phytosynergist combinations. P. polyxenes MFOs are 10 and 46 times less sensitive to inhibition by myristicin and safrole, respectively, than H. zea MFOs and eight times less sensitive to inhibition by safrole than MFOs from Papilio troilus, a closely related species that does not encounter furanocoumarin/phytosynergist combinations in its diet. Higher MFO activity and decreased sensitivity to MFO inhibitors are important adaptations that allow black swallowtail caterpillars to feed on many umbelliferous plants.