(<i>S</i>)‐norlaudanosoline synthase: The first enzyme in the benzylisoquinoline biosynthetic pathway

Rueffer, Martina; El-Shagi, H.; Nagakura, Naotaka; Zenk, Meinhart H.

doi:10.1016/0014-5793(81)80742-9

Cited by 76 publications

(60 citation statements)

References 19 publications

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“…Taken together, the previous data and those reported here are consistent with the concept of the existence of heterogeneous populations of vacuoles within the same plant that have specific roles with respect to alkaloid synthesis and storage. This is consistent with the differences of pH optima observed for the different enzymes of alkaloid synthesis (12)(13)(14)(15)17) as well as the differences in both the subcellular localization and uptake of thebaine and sanguinarine into vacuoles (6)(7)(8).…”

Section: Discussionsupporting

confidence: 73%

“…Dopa decarboxylase (13) and Snorlaudanosoline synthase (15,17), two enzymes involved in DA synthesis and transformation, are generally thought to be cytosolic, but the possibility that they are located in the same fragile vacuoles which contain DA cannot be ruled out. Earlier studies (6-8, 10, 16) suggest that different plants contain different types of vacuoles.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Subcellular Localization of Alkaloids and Dopamine in Different Vacuolar Compartments of Papaver bracteatum

Kutchan¹,

Rush²,

Coscia³

1986

Plant Physiol.

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Fractionation of Papaier bracteatum Arya II Lindl. latex on Renografin step gradients revealed that 43% of the dopamine was compartmentalized along with a-mannosidase (40%) in vacuoles sedimenting in the 2% fraction. Twenty-two percent of the dopamine was in the supernatant, but a corresponding amount (18%) of a-mannosidase was also present suggesting vacuole breakage during isolation. By subcellular fractionation of protoplasts from cultured P. bracteatum cells, the 1,000g sedimenting organelles have been identified as the major site of accumulation of the morphinan alkaloid, thebaine (99±@0.8%), and the benzophenanthridine alkaloid, sanguinarine (963%). Although the 1,000g pellet also contained 33±4% of the total alkaloid precursor, dopamine, and half of the total vacuolar marker enzyme, a-mannosidase, 62±10% of the amine was localized in the 100,000g supernatant. A differential distribution of the alkaloids was discovered upon resolution of the lysed protoplasts on Renografin step gradients. Over 40% of the dopamine was in the supernatant with 15% in a 2% Renografin band. The remainder was evenly distributed in denser fractions of the gradient. The 4 to 8% interface, previously found to contain the largest amount of thebaine and small amounts of sanguinarine and dopamine, has been shown to be enriched in vacuoles by electron microscopy. Using a histofluorescence method, dopamine compartmentation in vacuoles of intact cultured cells was corroborated. In summary, dopamine, sanguinarine, and thebaine occur in vacuoles of different densities. A large fraction of the total dopamine in cultured cells was found in the 100,000g supernatant along with 37% of the a-mannosidase suggesting that the amine may be sequestered in more fragile vacuoles than the alkaloids. The possibility that some dopamine may be cytosolic cannot be ruled out.The catecholamine, dopamine (2-(3,4-dihydroxyphenyl)-ethylamine), is a central intermediate in the biosynthesis of isoquinoline alkaloids in higher plants (18,19). It gives rise to both simple and l-benzyltetrahydroisoquinolines that are ultimately transformed into a broad spectrum of alkaloids. Recently, we discovered large amounts of dopamine (>1 mg/ml) in latex of Papaver bracteatum and P. somniferum (14). Furthermore, a small fraction of this dopamine (0.1 %) was localized in vacuoles of the same apparent density as those that sequester the morphinan alkaloids, thebaine, and morphine, in latex. This population of vacuoles was capable of alkaloid and dopamine transport by apparently independent mechanisms (6, 7). been well documented (10 and references cited therein). Whether the remainder of the endogenous dopamine was present in the cytosol, other organelles, or in larger and/or more fragile vacuoles was not resolved because of our inability to account for all of the original dopamine after lengthy differential and sucrose density gradient centrifugations.Analysis of P. bracteatum tissue cultures revealed large amounts of dopamine (up to 16% dry weight of the tissue) providi...

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Subcellular Localization of Alkaloids and Dopamine in Different Vacuolar Compartments of Papaver bracteatum

Kutchan¹,

Rush²,

Coscia³

1986

Plant Physiol.

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“…TIQ derivatives are thought to be biosynthesized from /3-phenethylamine derivatives and aldehyde or aldehyde-equivalent compounds by Pictet-Spenglertype condensation, which seems to be at least partially enzymatic in animals (Makino et al, 1990;Tasaki et al, 1993;Yamakawa and Ohta, 1997). 1BnTIQ and tetrahydropapaveroline, which was detected in urine from L-DOPA-treated parkinsonian patients (Sandler et al, 1973), were proposed to be biosynthesized from /3-phenethylamine and phenylacetaldehyde or dopamine and 3,4-dihydroxyphenylacetaldehyde, respectively (Sandler et al, 1973;Rueffer et al, 1981;Kotake et a!., 1995). That is, /3-phenethylamine and dopamine are each oxidized to aldehyde by monoamine oxidase [MAO; amine :oxygen oxidoreductase (deaminating; flavin-containing); EC 1.4.3.4], and condensed with their own metabolite to form 1BnTIQ and THP.…”

Section: Discussionmentioning

confidence: 99%

Novel Endogenous 1,2,3,4‐Tetrahydroisoquinoline Derivatives: Uptake by Dopamine Transporter and Activity to Induce Parkinsonism

Kawai

Makino

Hirobe

et al. 1998

Journal of Neurochemistry

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“…Next, we examined the substrate specificity of NCS, because (S)-norlaudanosoline, which is produced by the condensation of dopamine and 3,4-dihydroxyphenylacetaldehyde, was once thought to be a common pathway intermediate in benzylisoquinoline alkaloid biosynthesis (22,23), whereas (S)-norcoclaurine is now thought to be a natural precursor in benzylisoquinoline alkaloid biosynthesis (4,24). The substrate specificity of NCS was examined with several amines and aldehydes.…”

Section: Ncs Activity In C Japonica Cells-(s)-mentioning

confidence: 99%

Functional Analysis of Norcoclaurine Synthase in Coptis japonica

Minami

Dubouzet

Iwasa

et al. 2007

Journal of Biological Chemistry

126

111

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(S)-Norcoclaurine is the entry compound in benzylisoquinoline alkaloid biosynthesis and is produced by the condensation of dopamine and 4-hydroxyphenylacetaldehyde (4-HPAA) by norcoclaurine synthase (NCS) (EC 4.2.1.78). Although cDNA of the pathogenesis-related (PR) 10 family, the translation product of which catalyzes NCS reaction, has been isolated from Thalictrum flavum, its detailed enzymological properties have not yet been characterized. We report here that a distinct cDNA isolated from Coptis japonica (CjNCS1) also catalyzed NCS reaction as well as a PR10 homologue of C. japonica (CjPR10A). Both recombinant proteins stereo-specifically produced (S)-norcoclaurine by the condensation of dopamine and 4-HPAA. Because a CjNCS1 cDNA that encoded 352 amino acids showed sequence similarity to 2-oxoglutarate-dependent dioxygenases of plant origin, we characterized the properties of the native enzyme. Sequence analysis indicated that CjNCS1 only contained a Fe 2؉ -binding site and lacked the 2-oxoglutarate-binding domain. In fact, NCS reaction of native NCS isolated from cultured C. japonica cells did not depend on 2-oxoglutarate or oxygen, but did require ferrous ion. On the other hand, CjPR10A showed no specific motif. The addition of o-phenanthroline inhibited NCS reaction of both native NCS and recombinant CjNCS1, but not that of CjPR10A. In addition, native NCS and recombinant CjNCS1 accepted phenylacetaldehyde and 3,4-dihydroxyphenylacetaldehyde, as well as 4-HPAA, for condensation with dopamine, whereas recombinant CjPR10A could use 4-hydroxyphenylpyruvate and pyruvate in addition to the above aldehydes. These results suggested that CjNCS1 is the major NCS in C. japonica, whereas native NCS extracted from cultured C. japonica cells was more active and formed a larger complex compared with recombinant CjNCS1.Higher plants produce divergent chemicals such as alkaloids, terpenoids, and phenolic compounds in secondary metabolism. Among these chemicals, alkaloids are very important in medicine because of their high biological activities. Alkaloids are low molecular weight, nitrogen-containing compounds that are found in ϳ20% of plant species. Most alkaloids are derived from amines produced by the decarboxylation of amino acids such as histidine, lysine, ornithine, tryptophan, and tyrosine. Although the coupling of amines to other products is the first important step in producing diverse alkaloids, this entry reaction has been poorly characterized. (S)-Strictosidine is a central intermediate for indole alkaloids. Strictosidine synthase, which catalyzes the formation of (S)-strictosidine from tryptamine and secologanin, is a rare exception in that its cDNA has been cloned from Catharanthus roseus and Rauvolfia serpentine (1, 2).Benzylisoquinoline alkaloids are a large and diverse group of pharmaceutical alkaloids with ϳ2,500 defined structures. Norcoclaurine produced from tyrosine is a key entry compound from which various benzylisoquinoline alkaloids such as analgesic morphine, colchicines, antibacterial berberine...

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(S)‐norlaudanosoline synthase: The first enzyme in the benzylisoquinoline biosynthetic pathway

Cited by 76 publications

References 19 publications

Subcellular Localization of Alkaloids and Dopamine in Different Vacuolar Compartments of Papaver bracteatum

Subcellular Localization of Alkaloids and Dopamine in Different Vacuolar Compartments of Papaver bracteatum

Novel Endogenous 1,2,3,4‐Tetrahydroisoquinoline Derivatives: Uptake by Dopamine Transporter and Activity to Induce Parkinsonism

Functional Analysis of Norcoclaurine Synthase in Coptis japonica

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