Expression and characterization of the recombinant juvenile hormone epoxide hydrolase (JHEH) from Manduca sexta

Debernard, Stéphane; Morisseau, Christophe; Severson, Tonya F.; Feng, Li; Wojtasek, Hubert; Prestwich, Glenn D.; Hammock, Bruce D.

doi:10.1016/s0965-1748(98)00014-9

Cited by 44 publications

(39 citation statements)

References 44 publications

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“…3; Table 2). This group includes the well-known mammalian microsomal epoxide hydrolases (22) and the juvenile hormone epoxide hydrolases that are present in many insects (18). Group 5 is the best-defined group in the phylogenetic tree (Fig.…”

Section: Resultsmentioning

confidence: 99%

Diversity and Biocatalytic Potential of Epoxide Hydrolases Identified by Genome Analysis

Loo

Kingma

Arand

et al. 2006

Appl Environ Microbiol

108

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Epoxide hydrolases play an important role in the biodegradation of organic compounds and are potentially useful in enantioselective biocatalysis. An analysis of various genomic databases revealed that about 20% of sequenced organisms contain one or more putative epoxide hydrolase genes. They were found in all domains of life, and many fungi and actinobacteria contain several putative epoxide hydrolase-encoding genes. Multiple sequence alignments of epoxide hydrolases with other known and putative ␣/␤-hydrolase fold enzymes that possess a nucleophilic aspartate revealed that these enzymes can be classified into eight phylogenetic groups that all contain putative epoxide hydrolases. To determine their catalytic activities, 10 putative bacterial epoxide hydrolase genes and 2 known bacterial epoxide hydrolase genes were cloned and overexpressed in Escherichia coli. The production of active enzyme was strongly improved by fusion to the maltose binding protein (MalE), which prevented inclusion body formation and facilitated protein purification. Eight of the 12 fusion proteins were active toward one or more of the 21 epoxides that were tested, and they converted both terminal and nonterminal epoxides. Four of the new epoxide hydrolases showed an uncommon enantiopreference for meso-epoxides and/or terminal aromatic epoxides, which made them suitable for the production of enantiopure (S,S)-diols and (R)-epoxides. The results show that the expression of epoxide hydrolase genes that are detected by analyses of genomic databases is a useful strategy for obtaining new biocatalysts.Enantiopure epoxides and vicinal diols are valuable intermediates in the synthesis of a number of pharmaceutical compounds. Epoxide hydrolases (EC 3.3.2.3) catalyze the conversion of epoxides to the corresponding diols. If they are enantioselective, they can be used to produce enantiopure epoxides by means of kinetic resolution (5). In the past, when only epoxide hydrolases from mammalian sources were known (12), the use of epoxide hydrolases in biocatalysis was hampered by their poor availability and insufficient catalytic performance, such as a low turnover rate or poor enantioselectivity. The potential for biocatalytic application of epoxide hydrolases was significantly increased with the discovery of microbial epoxide hydrolases (41), which are easier to produce in large quantities. The cloning and overexpression of several enantioselective epoxide hydrolases, e.g., from Agrobacterium radiobacter (35), Aspergillus niger (3), and potato plants (40), not only facilitated large-scale production of these enzymes but also made it possible to improve their biocatalytic properties by site-directed or random mutagenesis (34,36,43).Since many microbial genome sequences are available in the public domain, it is useful to screen these databases for genes that might encode new enzymes with interesting properties.Novel epoxide hydrolases can be identified by performing a BLAST search of the genomic databases, using amino acid sequences of known epoxide hyd...

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Section: Resultsmentioning

confidence: 99%

Diversity and Biocatalytic Potential of Epoxide Hydrolases Identified by Genome Analysis

Loo

Kingma

Arand

et al. 2006

Appl Environ Microbiol

108

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“…These compounds are potential leads for the development of new therapeutic drugs for the treatment of epoxy-lipidinduced symptoms in conditions such as acute respiratory distress syndrome, which affects more than 150,000 individuals per year in the United States with Ͼ50% mortality (28). Similar pharmacophores likely will yield inhibitors of other epoxide hydrolases of importance in insects, plants, and mammals (2,29,30). As a cautionary note, however, high-level exposure to such therapeutic drugs or other inhibitors could alter both our normal inflammatory regulation and ability to transform xenobiotics.…”

Section: Discussionmentioning

confidence: 99%

Potent urea and carbamate inhibitors of soluble epoxide hydrolases

Morisseau

Goodrow

Dowdy

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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232

278

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The soluble epoxide hydrolase (sEH) plays a significant role in the biosynthesis of inf lammation mediators as well as xenobiotic transformations. Herein, we report the discovery of substituted ureas and carbamates as potent inhibitors of sEH. Some of these selective, competitive tightbinding inhibitors with nanomolar K i values interacted stoichiometrically with the homogenous recombinant murine and human sEHs. These inhibitors enhance cytotoxicity of transstilbene oxide, which is active as the epoxide, but reduce cytotoxicity of leukotoxin, which is activated by epoxide hydrolase to its toxic diol. They also reduce toxicity of leukotoxin in vivo in mice and prevent symptoms suggestive of acute respiratory distress syndrome. These potent inhibitors may be valuable tools for testing hypotheses of involvement of diol and epoxide lipids in chemical mediation in vitro or in vivo systems.Epoxide hydrolases (EH; E.C.3.3.2.3) catalyze the hydrolysis of epoxides or arene oxides to their corresponding diols by the addition of water (1). In mammals, the hepatic microsomal and soluble epoxide hydrolase forms are known to complement each other in detoxifying a wide array of mutagenic, toxic, and carcinogenic, xenobiotic epoxides (2, 3). Soluble EH (sEH) is also involved in the metabolism of arachidonic (4) and linoleic (5) acid epoxides. Arachidonate epoxides and diols are elevated in association with pregnancy-induced hypertension and modulate vascular permeability in the heart and kidneys (6). Diols derived from epoxy-linoleate (leukotoxin) perturb membrane permeability and calcium homeostasis (5), resulting in inflammation modulated by nitric oxide synthase and endothelin-1 (7, 8). Micromolar concentrations of leukotoxin reported in association with inflammation and hypoxia (9) depress mitochondrial respiration in vitro (10) and cause mammalian cardiopulmonary toxicity in vivo (7,11,12). Leukotoxin toxicity presents symptoms suggestive of multiple organ failure and acute respiratory distress syndrome (9). In both cellular and organismal models, leukotoxin-mediated toxicity depends on epoxide hydrolysis (5).The bioactivity of these epoxide hydrolysis products and their association with inflammation suggest that inhibition of vicinal-dihydroxylipid biosynthesis may have therapeutic value, making sEH a promising pharmacological target. Previously described selective sEH inhibitors, substituted chalcone oxides (as compound 1 in Table 1), and phenylglycidols (13,14) are epoxides that are hydrolyzed slowly by the target enzyme. Inhibition stems from an electronically stabilized covalent intermediate that results in low turnover and transient inhibition (15). Moreover, these compounds are relatively unstable, particularly in the presence of glutathione (13), making them of limited use in vivo. We describe herein the discovery of new potent and stable inhibitors of soluble EH and their application to both in vitro and in vivo models. MATERIALS AND METHODSSynthesis. Compounds 2, 3, 7-9, and 11-18 were obtained from Aldri...

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“…In insect, JH is principally degraded by two hydrolases, JH epoxide hydrolase (JHEH, EC 3.3.2.3) and JH esterase (JHE, EC 3.1.1.1) (Share and Roe, 1988;Debernard et al, 1998;Hirai et al, 2002;Maxwell et al, 2002a,b;Li et al, 2005;Zhang et al, 2005). JHEH belongs to the microsomal epoxide hydrolase family, and transforms epoxides to compounds with decreased chemical reactivity, increased water solubility, and altered biological activity (Arand et al, 2005;Morisseau and Hammock, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…A specific partition assay based on the inhibition of all of the JHE activity present in insect tissue extracts (Share and Roe, 1988) has been used to determine to which extent JHEH participates in JH degradation (Touhara and Prestwich, 1993;Wojtasek and Prestwich, 1996;Debernard et al, 1998). The assay reveals that JHEH is as critical as JHE in degrading JH in certain insects (Campbell et al, 1992;Halarnkar et al, 1993;Lassiter et al, 1995;Debernard et al, 1998). In the fourth larval instar of Culex quinquefasciatus, for example, JHEH activity is higher than JHE activity (Lassiter et al, 1995), implying its major function in JH degradation.…”

Section: Introductionmentioning

confidence: 99%

Characterization of two juvenile hormone epoxide hydrolases by RNA interference in the Colorado potato beetle

Lü

Guo

et al. 2015

Gene

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Expression and characterization of the recombinant juvenile hormone epoxide hydrolase (JHEH) from Manduca sexta

Cited by 44 publications

References 44 publications

Diversity and Biocatalytic Potential of Epoxide Hydrolases Identified by Genome Analysis

Diversity and Biocatalytic Potential of Epoxide Hydrolases Identified by Genome Analysis

Potent urea and carbamate inhibitors of soluble epoxide hydrolases

Characterization of two juvenile hormone epoxide hydrolases by RNA interference in the Colorado potato beetle

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