Epoxy allylic carbocations as conceptual intermediates in the biogenesis of diverse marine oxylipins

Gerwick, William H.

doi:10.1007/bf02587906

Cited by 55 publications

(40 citation statements)

References 68 publications

(126 reference statements)

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“…For example, Grechkin (7) noted that all three enzymes transform hydroperoxide substrate to an epoxy allylic carbocation intermediate that is resolved differently by each enzyme to yield different oxylipin products. The epoxy allylic cation intermediate is also proposed to play a central role in the biosynthesis of oxylipins found in marine organisms (57).…”

Section: Discussionmentioning

confidence: 99%

Molecular Cloning of a Divinyl Ether Synthase

Itoh

Howe

2001

Journal of Biological Chemistry

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Lipoxygenase-derived fatty acid hydroperoxides are metabolized by CYP74 cytochrome P-450s to various oxylipins that play important roles in plant growth and development. Here, we report the characterization of a Lycopersicon esculentum (tomato) cDNA whose predicted amino acid sequence defines a previously unidentified P-450 subfamily (CYP74D). The recombinant protein, expressed in Escherichia coli, displayed spectral properties of a P-450. The enzyme efficiently metabolized 9-hydroperoxy linoleic acid and 9-hydroperoxy linolenic acid but was poorly active against the corresponding 13-hydroperoxides. Incubation of recombinant CYP74D with 9-hydroperoxy linoleic acid and 9-hydroperoxy linolenic acid yielded divinyl ether fatty acids (colneleic acid and colnelenic acid, respectively), which have been implicated as plant anti-fungal toxins. This represents the first identification of a cDNA encoding a divinyl ether synthase and establishment of the enzyme as a CYP74 P-450. Genomic DNA blot analysis revealed the existence of a single divinyl ether synthase gene located on chromosome one of tomato. In tomato seedlings, root tissue was the major site of both divinyl ether synthase mRNA accumulation and enzyme activity. These results indicate that developmental expression of the divinyl ether synthase gene is an important determinant of the tissue specific synthesis of divinyl ether oxylipins.

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Section: Discussionmentioning

confidence: 99%

Molecular Cloning of a Divinyl Ether Synthase

Itoh

Howe

2001

Journal of Biological Chemistry

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“…4). The conversion of conjugated diene hydroperoxides to allyl carbocations like 3 has ample precedent, being implicated in the enzymatic synthesis of allene oxides, vinyl ethers, and other fatty acid derivatives (28), as well as related transformations of prostaglandin endoperoxides to prostacyclin and thromboxane A 2 (29). Removal of a proton from the carbocation 3 gives the leukotriene-type epoxide, product 2.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein–lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120

Schneider¹,

Niisuke²,

Boeglin³

et al. 2007

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

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Biological transformations of polyunsaturated fatty acids often lead to chemically unstable products, such as the prostaglandin endoperoxides and leukotriene A 4 epoxide of mammalian biology and the allene epoxides of plants. Here, we report on the enzymatic production of a fatty acid containing a highly strained bicyclic four-carbon ring, a moiety known previously only as a model compound for mechanistic studies in chemistry. Starting from linolenic acid (C18.33), a dual function protein from the cyanobacterium Anabaena PCC 7120 forms 9R-hydroperoxy-C18.33 in a lipoxygenase domain, then a catalase-related domain converts the 9R-hydroperoxide to two unstable allylic epoxides. We isolated and identified the major product as 9R,10R-epoxy-11trans-C18.1 containing a bicyclo[1.1.0]butyl ring on carbons 13-16, and the minor product as 9R,10R-epoxy-11trans,13trans,15cis-C18.3, an epoxide of the leukotriene A type. Synthesis of both epoxides can be understood by initial transformation of the hydroperoxide to an epoxy allylic carbocation. Rearrangement to an intermediate bicyclobutonium ion followed by deprotonation gives the bicyclobutane fatty acid. This enzymatic reaction has no parallel in aqueous or organic solvent, where ring-opened cyclopropanes, cyclobutanes, and homoallyl products are formed. Given the capability shown here for enzymatic formation of the highly strained and unstable bicyclobutane, our findings suggest that other transformations involving carbocation rearrangement, in both chemistry and biology, should be examined for the production of the high energy bicyclobutanes.catalase ͉ carbocation ͉ epoxide ͉ leukotriene ͉ bicyclobutonium ion

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“…Whereas the in vitro synthesis of these compounds in potato, garlic, and tomato extracts has been reported (Galliard and Phillips, 1972;Galliard et al, 1973;Grechkin et al, 1997;Caldelari and Farmer, 1998), divinyl ether fatty acids appear to be rare in nature. However, compounds of this type have been observed in some marine algae (Gerwick, 1996).…”

Section: Divinyl Ether Fatty Acid Production In Higher Plantsmentioning

confidence: 99%

Divinyl Ether Fatty Acid Synthesis in Late Blight–Diseased Potato Leaves

et al. 1999

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We conducted a study of the patterns and dynamics of oxidized fatty acid derivatives (oxylipins) in potato leaves infected with the late-blight pathogen Phytophthora infestans. Two 18-carbon divinyl ether fatty acids, colneleic acid and colnelenic acid, accumulated during disease development. To date, there are no reports that such compounds have been detected in higher plants. The divinyl ether fatty acids accumulate more rapidly in potato cultivar Matilda (a cultivar with increased resistance to late blight) than in cultivar Bintje, a susceptible cultivar. Colnelenic acid reached levels of up to ‫ف‬ 24 nmol (7 g) per g fresh weight of tissue in infected leaves. By contrast, levels of members of the jasmonic acid family did not change significantly during pathogenesis. The divinyl ethers also accumulated during the incompatible interaction of tobacco with tobacco mosaic virus. Colneleic and colnelenic acids were found to be inhibitory to P. infestans , suggesting a function in plant defense for divinyl ethers, which are unstable compounds rarely encountered in biological systems. INTRODUCTIONOxylipins (oxidized fatty acid derivatives) play diverse roles in plant biology as signal molecules for defense gene expression and as antimicrobial compounds (Hamberg and Gardner, 1992;Farmer, 1994). Many oxylipins are generated by the action of lipoxygenases. In plants, these enzymes add molecular oxygen to pentadiene fatty acids, such as linoleic acid and linolenic acid. The resultant products, fatty acid hydroperoxides, are subject to a diverse array of modifications leading to the generation of large numbers of other oxylipins whose functions have not been determined definitively.In plants, two carbon atoms in polyunsaturated 18-carbon fatty acids such as linoleic acid and linolenic acid are targets for the addition of molecular oxygen: C-13 and C-9. The metabolism of 13-hydroperoxylinolenic acid production has been studied in detail because it is metabolized to a family of potent biological regulators, the jasmonate family. Jasmonates regulate the expression of a number of genes necessary for the defense of plants against insect and microbial pathogens (Creelman and Mullet, 1997;Reymond and Farmer, 1998). A 13-lipoxygenase has been shown to be essential for wound-induced jasmonic acid (JA) synthesis in Arabidopsis (Bell et al., 1995). Another lipoxygenase in tobacco has been shown to be essential for defense of this plant against black shank disease (Rancé et al., 1998), although whether this lipoxygenase contributes to the synthesis of jasmonates or to other oxylipins in vivo is not known.With the aid of a method for the global analysis and quantitation of oxylipins, we recently discovered in potato and Arabidopsis tissues a new 16-carbon member of the JA family, known as dinor-oxo-phytodienoic acid (dnOPDA) (Weber et al., 1997;Farmer et al., 1998). The biological roles of fatty acid 9-hydroperoxides are far less clear. Although oxylipins derived from fatty acid 9-hydroperoxides have been characterized (Gardner, 1991...

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Epoxy allylic carbocations as conceptual intermediates in the biogenesis of diverse marine oxylipins

Cited by 55 publications

References 68 publications

Molecular Cloning of a Divinyl Ether Synthase

Molecular Cloning of a Divinyl Ether Synthase

Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein–lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120

Divinyl Ether Fatty Acid Synthesis in Late Blight–Diseased Potato Leaves

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