Sponsored by DuPont Crop Protection
Insect P450 paradox: Too simple as targets, too complicated as detoxifiers?
Dr. René Feyereisen is the recipient of the 2013 ACS International Award for Research in Agrochemicals. Dr. Feyereisen was born and grew up in The Hague. He received his Ph.D. degree from Louis Pasteur University in Strasbourg, France in 1979. After postdoctoral fellowships at the Agricultural Research Council at the University of Sussex and in the Department of Zoology at the University of Toronto, he served on the faculty of the Departments of Entomology and Agricultural Chemistry at Oregon State University (1981-1991) as the insect toxicologist. He moved to the University of Arizona as Professor of Entomology (1991-2000) and then joined the National Institute of Agronomical Research (INRA) at the Sophia Antipolis Research Center in France, where he is currently Director of Research.
Dr. Feyereisen’s early studies, initiated over 30 years ago, described the roles of cytochrome P450 enzymes in the biosynthesis of ecdysteroids and juvenile hormones (JH). His efforts began with the biochemical characterization of the enzymes, continued through the use of powerful inhibitors of JH biosynthesis and led to the molecular cloning and reconstitution of CYP15, the JH epoxidase. Feyereisen’s lab has also made major contributions to our understanding of factors underlying the physiological regulation of juvenile hormone titers through the discovery of allatostatins as “brain-gut” peptides, neuromodulators of juvenile hormone synthesis. His studies of the metabolism of hormones regulating insect development and metamorphosis have greatly enhanced our fundamental knowledge of these systems, calling attention to these insectspecific target sites.
In addition, Dr. Feyereisen is perhaps best well known for hisgroundbreaking research on the role of cytochrome P450 enzymes in insecticide detoxification and resistance. In the late 1980s, his lab was among the first to apply molecular technologies toward the study of enzymes involved in insecticide metabolism and was the first to clone an insect P450 enzyme and the first to succeed in the heterologous expression and reconstitution of the various components of the insect microsomal cytochrome P450 complex, NADPH cytochrome P450 reductase, cytochrome b5 and various P450s. The reconstituted system of purified enzymes provided clean biochemical evidence for the wide substrate specificity of a major house fly P450, CYP6A1, which was shown to be responsible for metabolism of (and resistance to) many insecticides.
Dr. Feyereisen has continued to pioneer the application of molecular genetic technologies in research that is of key importance to agrochemical toxicologists, including DNA microarrays or detox chips. These efforts have yielded a more complete understanding of the regulatory mechanisms leading to the constitutive overexpression of insecticide-metabolizing enzymes in resistant arthropods. Feyereisen’s work has increased our understanding of the evolution of the P450 gene family and these studies are especially relevant today, in an era when metabolic resistance has become a major impediment to the design and prolonged field use of pesticides.
In addition to his research, Dr. Feyereisen has written a number of influential reviews on JH biosynthesis, insecticide resistance, and on cytochrome P450 enzymes. He is currently co-editor of Insect Biochemistry and Molecular Biology, and has previously served on the editorial boards of Pesticide Biochemistry and Physiology, Archives of Insect Biochemistry and Physiology and on the Editorial Committee of Annual Review of Entomology. He co-chaired the 1997 Gordon Conference on Agricultural Science and served on the organizing committees of the IUPAC International Congresses of Pesticide Chemistry.