Specialized Enzymes in Insect Lipid Metabolism

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Authors

MacLean, Marina A.

Issue Date

2019

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Dissertation

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Cuticular hydrocarbons , CYP4G , Ips confusus , Ipsdienone reductase , Ipsenone , Pheromones

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Abstract

Insect pest management is a challenging problem across certain insect species. Mass attacks by pine bark beetles are difficult to control because beetles spend most of their life under the bark of trees and mass attacks often occur in remote regions. In other species, insecticide resistance has rendered several classes of insecticide obsolete. Development of novel targets is essential for insect management and control across all taxa. In this dissertation, I present results from experiments on specialized enzymes involved in lipid metabolism through two pathways, cuticular hydrocarbon biosynthesis and isoprenoid pheromone biosynthesis, pathways that provide unique targets for insecticides.Cuticular hydrocarbons are essential to insects in order to prevent water loss and also serve in chemical communication through contact pheromones. The final step in cuticular hydrocarbon biosynthesis is catalyzed by an insect specific cytochrome P450 from the CYP4G family. While most insects have two CYP4G genes, not all CYP4G gene products are hydrocarbon forming enzymes while other CYP4G enzymes appear to have dual functions. Here I show evidence that at least one CYP4G gene from each of <i>Musca domestica</i>, <i>Dendroctonus ponderosae</i>, <i>Anopheles gambiae</i>, and <i>Aedes aegypti</i> is involved in cuticular hydrocarbon biosynthesis. <i>Apis mellifera</i> is unique in that it has one CYP4G gene; it functions in hydrocarbon production. <i>D. ponderosae</i> has two CYP4G genes that appear to be involved in both hydrocarbon synthesis and pheromone production via the <i>exo</i>- brevicomin pathway.Chemical communication between insects is not restricted to non-volatile contact pheromones. Some insects rely on volatile chemicals to communicate over relatively long distances. Bark beetles from the <i>Ips</i> species use a combination of ipsdienol and ipsenol to coordinate mass attacks on host trees. The ratio and enantiomeric blends of ipsdienol and ipsenol differ between species and even with populations. Several enzymes in the monoterpenoid pathway have been characterized, however key enzymes in the pathway are yet to be discovered. A central intermediate in all ipsdienol and ipsenol biosynthetic pathways is ipsdienone. While oxidation of ipsdienol and ipsenol forms their respective ketones, it is not known how the carbon pool shifts from ipsdienone (with 3 carbon-carbon double bonds) to ipsenone (2 carbon-carbon double bonds). In this dissertation, I present evidence for a novel monoterpenoid carbon-carbon double bond reductase that catalyzes a central step in the ipsdienol and ipsenol biosynthesis. This enzyme, ipsdienone reductase (IDONER), converts ipsdienone to ipsenone, and is the first monoterpenoid carbon double bond reductase to be biochemically characterized in animals. Data in this dissertation allow for the prediction that at least one CYP4G in each species is involved in hydrocarbon production. In addition, reduction of ipsdienone by IDONER contributes to the final pheromone composition of <i>Ips</i> species. Future work to identify, model, and characterize other specialized enzymes in lipid metabolism will provide a map to understanding how insects have evolved the ability to simultaneously protect themselves and communicate, ultimately aiding in identification of targets for pest management.

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