Insects epoxide hydrolases

For a long time it was generally accepted that epoxide hydrolases are predominantly found in mammals [25,26], although epoxide hydrolase activities had been detected in bacteria [34,35] or fungi [36,37] quite some years ago. This view was too simplistic, since these enzymes have now been detected in many bacteria [38-40], fungi [41], as well as in red yeast [42]. Moreover, epoxide hydrolase activity has also been demonstrated in plants [43] and insects [44]. 

The existence of a cytosolic epoxide hydrolase was first indicated by its ability to hydrolyze analogs of insect juvenile hormone not readily hydrolyzed by microsomal epoxide hydrolase. Subsequent studies demonstrated a unique cytosolic enzyme catalytically and structurally distinct from the microsomal enzyme. It appears probable that the cytosolic enzyme is peroxisomal in origin. Both enzymes are broadly nonspecific and have many substrates in common. It is clear, however, that many substrates hydrolyzed well by cytosolic epoxide hydrolase are hydrolyzed poorly by microsomal epoxide hydrolase and vice versa. For example, l-(4 -ethylphenoxy)-3,7-dimethy I -6,7-epoxy-//7//i,v-2-octene, a substituted geranyl epoxide insect juvenile hormone mimic, is hydrolyzed 10 times more rapidly by the cytosolic enzyme than by the microsomal one. In any series, such as the substituted styrene oxides, the trans configuration is hydrolyzed more rapidly by the cytosolic epoxide hydrolase than is the cis isomer. At the same time, it should remembered that in this and other series,... 

From the aforementioned findings, it is clear that insect cuticle contains various detoxification enzymes, including DDT-dehydrochlorinase, epoxide hydrolase, and cytochrome P450 monooxygenases. 

Epoxide rings of alkene and arene compounds are hydrated to form trans-diols. The enzymes that catalyze the addition of a molecule of water to an epoxide ring to yield diols are called epoxide hydrolases (also known as epoxide hydrases). Epoxide hydrolase activity has been detected in numerous species of insects. Enzymatic epoxide hydration of certain cyclodiene insecticides and their analogs has been demonstrated in the housefly, blowfly (Calliphora erythrocephala), yellow mealworm (Tenebrio molitor), Madagascar cockroach (Gromphadorhina portentosa), southern army worm (Spodoptera eridania), and red flour beetle (Tribolium castaneum). Epoxide hydrolase is also important in the metabolism of juvenile... 

Methyl esters prepared from undecylenic acid and containing an episulfide group were tested as inhibitors of JH III epoxide hydrolase activity to evaluate its biological role in insects <2005MI140>. 

The failure of the artificially high titers of JHE to disrupt larval development may be due to several factors. Since the reduction in JHE is mediated by a variety of events, one can predict that for recombinant JHE to be effective, levels in the hemolymph must greatly exceed those normally present in the last larval instar. In normal larvae JH metabolism by esterase and epoxide hydrolase is high in most tissues while in infected larvae JHE levels increase in the hemolymph and infected, but presumably not uninfected tissues. Thus tissue levels of JH may not decrease sufficiently to induce metamorphosis. Since epoxide hydrolase levels are not affected there is also the possibility that JH acid may be remethylated to an active form in some tissues. The JH binding protein is hypothesized to increase the degradation of JH in the presence of JHE by keeping the JH in a pool accessible to the enzyme. However, the titers of JH binding protein in infected insects are not known. 

Kamita, S.G., Oshita, G.H., Wang, P., Morisseau, C., Hammock, B.D., Nandety, R.S. and Falk, B.W. (2013) Characterization of Hovi-mEHl, a microsomal epoxide hydrolase from the glassy-winged sharpshooter Honudodisca vitripennis. Arch. Insect Biochem. Physiol., 83, 171-179. 

Over the past few years, several purified membrane-bound and soluble epoxide hydrolases from various origin have been (at least partially) sequenced. Some of them have also been cloned and overexpressed. This is the case for the soluble epoxide hydrolase from rat liver that has been overexpressed in E. coli [73,74]. Other epoxide hydrolase genes that have been cloned so far are of mammalian [73,75-78], insect [42], plant [79,80], and one of bacterial [81] origin. 

Both enantiomers of Bower s compound, a potent analog of an insect juvenile hormone [161] (Scheme 20), were prepared in 96% e.e. using A. niger epoxide hydrolase. Interestingly, subsequent biological tests revealed that the (6R) antipode was about 10 times more active than the (6S) conterpart against the yellow mealworm Tenebrio molitor. 

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