Functional Significance of Variation in CYP6B4 in Papilio glaucus

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9630442 Berenbaum Cytochrome P450 monooxygenases are enzymes involved in the metabolism of foreign compounds in organisms ranging from bacteria to humans. Despite their virtually universal distribution, little is known about the functional significance of variation in these enzymes. This gap in knowledge is particularly acute with respect to P450s in insects, despite the importance of these enzymes in the metabolism of plant toxins as well as insecticides. In the tiger swallowtail, Papilio glaucus, CYP6B4 is known to metabolize furanocoumarins, plant secondary substances that are toxic to a wide variety of insects. Unlike its relatives, which feed exclusively on plants containing furanocoumarins, the tiger swallowtail almost never encounters these toxins in its host plants. In this project, the investigators will examine variation in the structure and function of CYP6B4 in relation to the frequency with which furanocoumarins are encountered in the diet of the tiger swallowtail. By examining variation in enzyme function in the presence and absence of naturally occurring toxins, we hope to gain insight into the process by which plant-feeding insects develop the metabolic capability to feed on toxic plants as well as into the process by which cytochrome P450s assume importance in the acquisition of resistance to insecticides and other synthetic toxins.