Phytodienoic acid

Figure 8.6 A diagram of the oxylipin pathway. LOX lipoxygenase AOS allene oxide synthase HPL hydroperoxide lyase AOC allene oxide cyclase OPDA Reductase 12-oxo-phytodienoic acid-10,11-reductase.

The alcohol moiety is produced in a different manner from that of the acid moiety. The alcohol moiety resembles the plant hormone jasmonic acid (JA) (26) generated from linolenoyl moiety of lipids via (13,S )-hydroperoxy-linolenic acid (22), (12.13,S )-epoxylinolenic acid (23), and 12-oxo-cis-10.15-phytodienoic acid (24) by the oxylipin or octadecanoid pathway (Fig. 3) [31]. In fact, 13C was incorporated at pyrethrolone (1) carbon positions that agreed with those predicted to be labeled when the alcohol moiety is produced via the pathway (Fig. 3) [30]. Figure 3 illustrates that m-jasmone (25) is hydroxylated to yield jasmololone (4), which is then dehydrogenated to yield pyrethrolone (5). However, it has not yet been determined if this is actually the case. 

The most well known and well investigated degradation reaction of 13S-HPOTE is the generation of jasmonic acid. 13S-HPOTE is converted by allene oxide hydroperoxydehydrase by an intramolecular elimination of water to an allene oxide [160]. The latter is cyclized by allene oxide cyclase to 9S,13S,12-oxo-10,15-phytodienoic acid [160] followed by a trifold P-oxidation and a hydrogenation step (Scheme 7) [108]. 

Fig. 8. Metabolism of 18 3 fatty acid to oxylipins. I. Lipoxygenase 2, alleneoxide synthase 3, allene oxide cyclase 4, 12-oxo-phytodienoic acid reductase, -oxidation 5, hydroperoxide lyase.

The key intermediate product in the biosynthetic pathway is 8-[2-(c -pent-2 -enyl)-3-oxo-cw-cyclopent-4-enyI]octanoic acid (12-oxo-c/s-10,15-phytodienoic acid ... 

Schierle, K., J. Hopke, M.L. Niedt, W. Boland, and E. Steckhan, Homologues of Dihydro-12-oxo-phytodienoic Acid and Jasmonic Acid by Mixed Kolbe Electrolysis, Tetrahedron Lett. 37 8715-8718 (1996). 

Jasmonic acid is derived from a-linolenic acid, 13(5)-hydroperoxylinolenic acid, 12-oxophytodienoic acid, and phytodienoic acid (Farmer and Ryan, 1990, 1992 Hamberg and Gardner, 1992). The biosynthesis of jasmonic acid and related compounds has been reviewed (Sembdner and Parthier, 1993). 

Hydroxy-4-oxo-5- 2-pentenyl)-1-cycloperitene-1 -octanoic acid. 13-Hydroxy-12-0X0-9,15-phytodienoic acid [81905-33-1]... 

Hydroxy-3-oxo-2- 2-pentenyl)-l-cyclopentene-1-octanoic acid, 9C1. 11-Hydroxy-12-oxo-9 l3),15-phytodienoic acid [82451-23-8]... 

Flaxseed contains a hydroperoxide isomerase converting the 13-hydroperoxide from linolenic acid to 13-hydroxy-12-oxo-18 2( 9, 15), 12-oxo-lO,15-phytodienoic acid (56) and some 9-hydroxy-12-oxo-18 2(10,15). The 9-hydroperoxide furnishes 9-hydroxy-lO-oxo-18 2(12,15) and some 13-hydroxy-10-oxo-18 2(115,15z).The... 

Recently, it has been shown that H-oxo-cm-IO, 15-phytodienoic acid is formed when a-linolenic acid is incubated with an extract of flaxseed powder in the presence of molecular oxygen (Zimmerman and Feng, 1978 Vick et al., 1979). Initially, the action of a lipoxygenase leads to formation of the well-known 13-L-hydroxyperoxy-cij, cis-9, 15-tra/is-ll-octatrienoic acid, a portion of which is converted by hydroperoxide isomerase to an a-ketol, whereas another portion is cyclized, through enzymatic action, to the 0x0-phytodienoic acid mentioned above (Vick and Zimmerman, 1979b). The sequence of reactions leading to this cyclic fatty acid is shown in Fig. 8. 

Fig. 8. Biosynthesis of 12-oxo-cu-10,lS-phytodienoic acid from a-linolenic acid.

More than 30 years ago it was reported that flaxseed homogenates convert 13-HpOTrE into a- and -y-ketols, and the enzyme responsible for this reaction was called hydroperoxide isomerase [54]. Later studies indicated that this reaction was actually a two-step process, consisting of an enzyme-catalysed dehydration of the hydroperoxy fatty acid to a rather unstable allene oxide followed by a non-enzymic hydrolysis [55,56]. The enzyme responsible for allene oxide synthesis has been purified and shown to be a cyt E-450 isoform [57]. As an alternative to hydrolysis, the allene oxide may undergo enzymic cyclization forming 12-oxo-phytodienoic acid. This compound is subsequently converted into jasmonic acid, a phytohormone implicated in the reaction of higher plants to a number of stimuli, such as wounding, fungal elicitation, mechanical forces and osmotic stress [54]. 

The last route is important for the formation of jasmonic acid. The action of allene oxide synthase on 13-hydroperoxy linolenic acid initially results in the generation of 12,13-epoxy-octadecatrienoic acid. This unstable epoxide is either chemically hydrolyzed to a- and y-ketols and racemic 12-oxo-phytodienoic acid or, in the presence of allene oxide cyclase (AOC), is further converted to enantiomeric pure 12-oxo-PDA [7]. The ring double bond of PDA is then reduced in a NADPH dependent reaction by 12-oxo-PDA reductase and after shortening of the side chain containing the carboxy group by 3 rounds of fi>-oxidation, the biosynthesis of jasmonic acid is completed. 

Fig, 1 Schematic representation of the octadecanoid pathway leading to jasmonic acid biosynthesis. 12-OH-JA, 12-hydroxy-jasmonic acid AOC, allene oxide cyclase AOS, allene oxide synthase JA, jasmonic acid JARl, enzyme responsible for the conjugation of JA with isoleucine (JA-Ile) JMT, 5 -adenosyl-L-methionine jasmonic acid carboxyl methyl transferase LA, a-linolenic acid LOX, lipoxygenase MeJA, methyl jasmonate OPDA, 12-oxo-phytodienoic acid OPR3, OPDA reductaseS PL, phospholipase... 

NLS neutral loss scan or scanning NMR nuclear magnetic resonance OPDA oxo-phytodienoic acid PA phosphatidic acid PC choline glycerophospholipid(s)... 

Allene oxide synthase route. Allene oxide synthase dehydrates hydroperoxides, affording allene oxide fatty acids, Allene oxides are rapidly hydrolyzed into ketols [2,6]. Allene oxide, corresponding to 13-HPOT, along with hydrolysis undergoes cyclization, affording cyclopentenone 12-oxo-10,15(Z)-phytodienoic acid. The last upon its reduction and j8-oxidation is converted into jasmonic acid ... 

Taki N, SasaM-Sekimoto Y, Obayashi T, Kikuta A, Kobayashi K, Ainai T, Yagi K, Seikuiai N, Suzuki H, MasudaT, K-IT, ShibataD, Kobayashi Y, Ohta H (2005) 12-Oxo-phytodienoic acid triggers expression of a distinct set of genes and plays a role in wound-induced gene expression... 

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