Biosynthesis of 8-R-HPETE and preclavulone-A from arachidonate in several species of caribbean coral. A widespread route to marine prostanoids.

Corey, E. J.; Matsuda, Seiichi P. T.; Nagata, Ryu; Cleaver, Martin B.

doi:10.1016/s0040-4039(00)86110-9

Cited by 77 publications

(29 citation statements)

References 10 publications

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“…By analogy to the plant CYP74 P450 family that metabolize fatty acid hydroperoxides, such homologues could exhibit AOS, hydroperoxide lyase, epoxyalcohol synthase, or divinyl ether synthase activities (6). Whether residing in fusion proteins or as autonomous polypeptides, 8R-LOX and AOS activities are ubiquitous in corals (5,33,34), and their expression will likely be detected in other invertebrates (35). Other homologues of the AOS domain suggest expanded roles.…”

Section: The Chemical Nature Of the U-shaped Cavity Is Complementary mentioning

confidence: 99%

“…The prostaglandins are formed from arachidonic acid via a conventional cyclooxygenase route (1,2), yet the overwhelming catalytic activity evident in coral extracts is lipoxygenase (LOX) pathway metabolism (3). Arachidonic acid is converted to an 8R-hydroperoxide that is further transformed to an allene oxide (epoxide) (3)(4)(5). This pathway bears many parallels with the route of jasmonic acid biosynthesis in plants ( Fig.…”

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confidence: 98%

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The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

Oldham

Brash

Newcomer

2004

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

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8R-Lipoxygenase and allene oxide synthase (AOS) are parts of a naturally occurring fusion protein from the coral Plexaura homomalla. AOS catalyses the production of an unstable epoxide (an allene oxide) from the fatty acid hydroperoxide generated by the lipoxygenase activity. Here, we report the structure of the AOS domain and its striking structural homology to catalase. Whereas nominal sequence identity between the enzymes had been previously described, the extent of structural homology observed was not anticipated, given that this enzyme activity had been exclusively associated with the P450 superfamily, and conservation of a catalase fold without catalase activity is unprecedented. Whereas the heme environment is largely conserved, the AOS heme is planar and the distal histidine is flanked by two hydrogen-bonding residues. These critical differences likely facilitate the switch from a catalatic activity to that of a fatty acid hydroperoxidase.eicosanoids ͉ heme

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Section: The Chemical Nature Of the U-shaped Cavity Is Complementary mentioning

confidence: 99%

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confidence: 98%

The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

Oldham

Brash

Newcomer

2004

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

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“…This unstable epoxide is acted upon by the enzyme allene oxide cyclase (AOC) to produce a chiral cyclopentenone, a few steps away from the end product, jasmonic acid. In coral, the lipoxygenase precursor is the 8R-hydroperoxide of arachidonic acid, which is transformed by a catalase-related hemoprotein to the 8,9-epoxy allene oxide, a presumed precursor of the clavulones and related cyclopentenones of corals (7,8). Recently, an allene oxide formed from 12R-hydroperoxy linolenic acid by a cyanobacterial catalase-related enzyme was described (9).…”

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confidence: 99%

Isolation and Characterization of Two Geometric Allene Oxide Isomers Synthesized from 9S-Hydroperoxylinoleic Acid by Cytochrome P450 CYP74C3

Brash¹,

Boeglin²,

Stec

et al. 2013

Journal of Biological Chemistry

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Background: Allene oxides involved in cyclopentenone biosynthesis are extremely labile and have eluded full stereochemical assignment. Results: We identify a novel Z-allene oxide that unexpectedly rearranges to a cyclopentenone. Conclusion: Other natural allene oxides are assigned the E configuration and can be easily distinguished from the Z-allene oxide by NMR. Significance: Unequivocal determination of the unknown allene oxide configuration is documented and helps elucidate the cyclization chemistry.

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“…Although it has proved difficult to detect prostaglandin synthesis using in vitro preparations of P. homomalla, the metabolism of added arachidonic acid is readily observed (2,5). There is very high 8R-lipoxygenase activity, sufficient to consume perhaps 1 mM arachidonic acid in a 1:10 tissue/buffer homogenate.…”

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confidence: 99%

“…Biosynthesis has been detected in both plants and marine invertebrates (8,9). Allene oxides can cyclize to form five-membered carbon rings, and initially this was suspected to be part of the coral route to the prostaglandins (2,5). In plants, the enzymatic cyclization of an allene oxide derived from 13-hydroperoxylinolenic acid is established as a step in biosynthesis of the cyclopentanone hormone, jasmonic acid (10).…”

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confidence: 99%

Purification and Catalytic Activities of the Two Domains of the Allene Oxide Synthase-Lipoxygenase Fusion Protein of the CoralPlexaura homomalla

Boutaud

Brash

1999

Journal of Biological Chemistry

100

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The conversion of fatty acid hydroperoxides to allene epoxides is catalyzed by a cytochrome P450 in plants and, in coral, by a 43-kDa catalase-related hemoprotein fused to the lipoxygenase that synthesizes the 8R-hydroperoxyeicosatetraenoic acid (8R-HPETE) substrate. We have expressed the separate lipoxygenase and allene oxide synthase (AOS) domains of the coral protein in Escherichia coli (BL21 cells) and purified the proteins; this system gives high expression (1.5 and 0.3 mol/liter, respectively) of catalytically active enzymes. Both domains show fast reaction kinetics. Catalytic activity of the lipoxygenase domain is stimulated 5-fold by high concentrations of monovalent cations (500 mM Na ؉ , Li ؉ , or K ؉ ), and an additional 5-fold by 10 mM Ca 2؉ . The resulting rates of reaction are Ϸ300 turnovers/s, 1-2 orders of magnitude faster than mammalian lipoxygenases. This makes the coral lipoxygenase well suited for partnership with the AOS domain, which shows maximum rates of Ϸ1400 turnovers/s in the conversion of 8R-HPETE to the allene oxide. Some unusual catalytic activities of the two domains are described. The lipoxygenase domain converts 20.36 partly to the bis-allylic hydroperoxide (10-hydroperoxyeicosa-8,11,14-trienoic acid). Metabolism of the preferred substrate of the AOS domain, 8R-HPETE, is inhibited by the enantiomer 8S-HPETE. Although the AOS domain has homology to catalase in primary structure, it is completely lacking in catalatic action on H 2 O 2 ; catalase itself, as expected from its preference for small hydroperoxides, is ineffective in allene oxide synthesis from 8R-HPETE.

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Biosynthesis of 8-R-HPETE and preclavulone-A from arachidonate in several species of caribbean coral. A widespread route to marine prostanoids.

Cited by 77 publications

References 10 publications

The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

Isolation and Characterization of Two Geometric Allene Oxide Isomers Synthesized from 9S-Hydroperoxylinoleic Acid by Cytochrome P450 CYP74C3

Purification and Catalytic Activities of the Two Domains of the Allene Oxide Synthase-Lipoxygenase Fusion Protein of the CoralPlexaura homomalla

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