Demonstration that limonene is the first cyclic intermediate in the biosynthesis of oxygenated p-menthane monoterpenes in Mentha piperita and other Mentha species

Kjonaas, Robert; Croteau, Rodney

doi:10.1016/0003-9861(83)90389-2

Cited by 99 publications

(35 citation statements)

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“…All enzyme preparations were derived from leaf epidermis extracts (7) since the glandular trichomes appear to be the exclusive sites of monoterpene biosynthesis and the relevant enzymes thus far examined are restricted to these structures (7,8). The results of these enzyme-level studies are tabulated (Table II), and each enzymatic step is described below in sequence, starting with the formation of (-)-limonene which is the parent olefin for monoterpene biosynthesis in both peppermint and spearmint species (13).…”

Section: Enzyme Activity Measurementsmentioning

confidence: 99%

“…Production of either the C3-oxygenated family or the C6-oxygenated type is considered to be under the control of a single gene (25). This regiospecificity of oxygenation is established very early in the monoterpene biosynthetic sequence where (-)-limonene, the first cyclic olefin to arise from the ubiquitous isoprenoid precursor geranyl pyrophosphate, is hydroxylated exclusively at C3 to (-)-trans-isopiperitenol (in peppermint) or at C6 to (-)-transcarveol (in spearmint) (13). The Cyt P-450-dependent mixed function oxygenases responsible for these transformations have been isolated from peppermint and spearmint and partially characterized (12).…”

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confidence: 99%

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Biochemical Characterization of a Spearmint Mutant That Resembles Peppermint in Monoterpene Content

Croteau¹,

Karp²,

Wagschal³

et al. 1991

Plant Physiol.

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A radiation-induced mutant of Scotch spearmint (Mentha x graclis) was shown to produce an essential oil containing principally C3-oxygenated p-menthane monoterpenes that are typical of peppermint, instead of the CS-oxygenated monoterpene family characteristic of spearmint. In vitro measurement of all of the enzymes responsible for the production of both the C3-oxygenated and CS-oxygenated families of monoterpenes from the common precursor (-)-limonene indicated that a virtually identical complement of enzymes was present in wild type and mutant, with the exception of the microsomal, cytochrome P-450-dependent (-)-limonene hydroxylase; the C6-hydroxylase producing (-)-trans-carveol in the wild type had been replaced by a C3-hydroxylase producing (--trans-isopiperitenol in the mutant. Additionally, the mutant, but not the wild type, could carry out the cytochrome P-450-dependent epoxidation of the ai-unsaturated bond of the ketones formed via C3-hydroxylation. Although present in the wild type, the enzymes of the C3-pathway that convert trans-isopiperitenol to menthol isomers are synthetically inactive because of the absence of the key C3-oxygenated intermediate generated by hydroxylation of limonene. These results, which clarify the origins of the C3-and CS-oxygenation patterns, also allow correction of a number of earlier biogenetic proposals for the formation of monoterpenes in Mentha.The monoterpene constituents of the essential oils of peppermint (Mentha piperita L.) and spearmint (native = Mentha spicata L.; Scotch = Mentha x gracilis [28]) are distinguished by the position of oxygenation on the p-menthane ring3 (18,25). Peppermint produces almost exclusively monoterpenes bearing an oxygen function at C3, such as menthone and menthol, whereas spearmint species produce almost exclusively monoterpenes bearing an oxygen function at C6, typi-

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Section: Enzyme Activity Measurementsmentioning

confidence: 99%

mentioning

confidence: 99%

Biochemical Characterization of a Spearmint Mutant That Resembles Peppermint in Monoterpene Content

Croteau¹,

Karp²,

Wagschal³

et al. 1991

Plant Physiol.

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“…Menthol biosynthesis ( Fig. 1) begins with the diversion of the primary isoprenoid intermediates, isopentenyl diphosphate and its allylic isomer, dimethylallyl diphosphate, to geranyl diphosphate (the precursor of all monoterpenes) by the prenyltransferase geranyl diphosphate synthase (GPPS; Burke et al, 1999), and is followed by ionization and cyclization of this C 10 intermediate to limonene by the terpene cyclase (2)-(4S)-limonene synthase (Kjonaas and Croteau, 1983). Regiospecific and stereospecific hydroxylation of this monoterpene olefin intermediate is catalyzed by cytochrome P450 limonene-3-hydroxylase to yield (2)-trans-isopiperitenol and is followed by dehydrogenation of this allylic alcohol (by isopiperitenol dehydrogenase) to afford the a,b-unsaturated ketone (-)-isopiperitenone.…”

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Monoterpene Metabolism. Cloning, Expression, and Characterization of Menthone Reductases from Peppermint

et al. 2005

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(−)-Menthone is the predominant monoterpene produced in the essential oil of maturing peppermint (Mentha x piperita) leaves during the filling of epidermal oil glands. This early biosynthetic process is followed by a second, later oil maturation program (approximately coincident with flower initiation) in which the C3-carbonyl of menthone is reduced to yield (−)-(3R)-menthol and (+)-(3S)-neomenthol by two distinct NADPH-dependent ketoreductases. An activity-based in situ screen, by expression in Escherichia coli of 23 putative redox enzymes from an immature peppermint oil gland expressed sequence tag library, was used to isolate a cDNA encoding the latter menthone:(+)-(3S)-neomenthol reductase. Reverse transcription-PCR amplification and RACE were used to acquire the former menthone:(−)-(3R)-menthol reductase directly from mRNA isolated from the oil gland secretory cells of mature leaves. The deduced amino acid sequences of these two reductases share 73% identity, provide no apparent subcellular targeting information, and predict inclusion in the short-chain dehydrogenase/reductase family of enzymes. The menthone:(+)-(3S)-neomenthol reductase cDNA encodes a 35,722-D protein, and the recombinant enzyme yields 94% (+)-(3S)-neomenthol and 6% (−)-(3R)-menthol from (−)-menthone as substrate, and 86% (+)-(3S)-isomenthol and 14% (+)-(3R)-neoisomenthol from (+)-isomenthone as substrate, has a pH optimum of 9.3, and K m values of 674 μ m, > 1 mm, and 10 μ m for menthone, isomenthone, and NADPH, respectively, with a k cat of 0.06 s−1. The recombinant menthone:(−)-(3R)-menthol reductase has a deduced size of 34,070 D and converts (−)-menthone to 95% (−)-(3R)-menthol and 5% (+)-(3S)-neomenthol, and (+)-isomenthone to 87% (+)-(3R)-neoisomenthol and 13% (+)-(3S)-isomenthol, displays optimum activity at neutral pH, and has K m values of 3.0 μ m, 41 μ m, and 0.12 μ m for menthone, isomenthone, and NADPH, respectively, with a k cat of 0.6 s−1. The respective activities of these menthone reductases account for all of the menthol isomers found in the essential oil of peppermint. Biotechnological exploitation of these genes could lead to improved production yields of (−)-menthol, the principal and characteristic flavor component of peppermint.

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“…Monoterpene biosynthesis and accumulation in mint has been specifically localized to the glandular trichomes (Gershenzon et al, 1989;McCaskill et al, 1992). The pathway originates in the plastids (leucoplasts) of the secretory cells of these highly specialized, non-photosynthetic glandular structures (Turner et al, 1999) because both the universal acyclic precursor geranyl diphosphate (Burke et al, 1999) and the first committed intermediate of the pathway (Ϫ)-limonene (Kjonaas and Croteau, 1983;Colby et al, 1993;Turner et al, 1999) are now known to arise from primary metabolism at this locale. The first cyclic intermediate (Ϫ)-limonene subsequently undergoes cytochrome P450-catalyzed hydroxylation to (Ϫ)-trans-isopiperitenol at the endoplasmic reticulum (ER) (Karp et al, 1990;Lupien et al, 1999), and the remaining transformations, comprising largely redox metabolism (Fig.…”

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Development of Peltate Glandular Trichomes of Peppermint

Turner¹,

Gershenzon²,

Croteau³

2000

Plant Physiol.

211

176

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Cryofixation and conventional chemical fixation methods were employed to examine the ultrastructure of developing peltate glandular trichomes of peppermint (Mentha ϫ piperita). Our results are discussed in relation to monoterpene production and the mechanism of essential oil secretion. Peltate glands arise as epidermal protuberances (initials) that divide asymmetrically to produce a vacuolate basal cell, a stalk cell, and a cytoplasmically dense apical cell. Further divisions of the apical cell produce a peltate trichome with one basal cell, one stalk cell, and eight glandular (secretory) disc cells. Presecretory gland cells resemble meristematic cells because they contain proplastids, small vacuoles, and large nuclei. The secretory phase coincides with the separation and filling of the sub-cuticular oil storage space, the maturation of glandular disc cell leucoplasts in which monoterpene biosynthesis is known to be initiated, and the formation of extensive smooth endoplasmic reticulum at which hydroxylation steps of the monoterpene biosynthetic pathway occur. The smooth endoplasmic reticulum of the secretory cells appears to form associations with both the leucoplasts and the plasma membrane bordering the sub-cuticular oil storage cavity, often contains densely staining material, and may be involved with the transport of the monoterpene-rich secretion product. Associated changes in the ultrastructure of the secretory stage stalk cell are also described, as is the ultrastructure of the fragile post-secretory gland for which cryofixation methods are particularly well suited for the preservation of organizational integrity.

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Demonstration that limonene is the first cyclic intermediate in the biosynthesis of oxygenated p-menthane monoterpenes in Mentha piperita and other Mentha species

Cited by 99 publications

References 31 publications

Biochemical Characterization of a Spearmint Mutant That Resembles Peppermint in Monoterpene Content

Biochemical Characterization of a Spearmint Mutant That Resembles Peppermint in Monoterpene Content

Monoterpene Metabolism. Cloning, Expression, and Characterization of Menthone Reductases from Peppermint

Development of Peltate Glandular Trichomes of Peppermint

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