Indole Alkaloid Biosynthesis Research Articles

モノテルペン配糖体及び関連天然物の研究(第52報)セコイリドイド配糖体, インドールアルカロイドの生合成において鎖状テルペンよりイリダン骨格が形成される機構について

Administration of various 3H-labeled monoterpenes to Catharanthus roseus and Lonicera morrowii demonstrated that secoiridoid glucosides and indole alkaloids of these plants are formed through cyclization of 10-oxoneral or 10-oxogeranial to iridodial followed by further elaboration. This result is contradictory with the report by Kurz et al. which indicated the intermediacy of 9, 10-dihydroxygeraniol and its oxo-derivatives for the biosynthesis of secologanin and indole alkaloids of C. roseus suspension cultures.

Selection of Cell Lines of Catharanthus roseus with Increased Tryptophan Decarboxylase Activity

Cell lines of Catharcmthus roseus were selected for resistance to 4-methyltryptophan (4-MT) in order to get strains with increased activities of tryptophan decarboxylase (TDC). This enzyme may exert a decisive regulatory control in indole alkaloid biosynthesis. 4-Methyltryptophan is a substrate for TDC and is detoxified by this enzyme. All 4-MT resistant cell lines showed increased TDC activity (3-to 10-fold) and higher accumulation of tryptamine (3- to 5-fold). Two of these cell lines with increased TDC activity accumulated indole alkaloids in the growth medium, whereas in wild type cultures and other resistant cell lines this was not the case. All the cell lines obtained were not only resistant to 4-MT (20- to 70-times more than wild type cells) but were also cross-resistant to other tryptophan analogues which are not metabolized by TDC. Therefore the resistance was not only due to a better detoxification of the analogue. The selected cell lines also contained 2 to 6 times higher levels of ʟ-tryptophan but the feedback sensitivity of the anthranilate synthetase of the resistant cells was not alteref

Secologanin, a Biogenetic Key Compound—Synthesis and Biogenesis of the Iridoid and Secoiridoid Glycosides

AbstractThe monoterpene glycoside secologanin is a key intermediate in the biosynthesis of most indole, cinchona, ipecacuanha, and pyrroloquinoline alkaloids, as well as of simple monoterpene alkaloids. More than a thousand alkaloids are formed from secologanin in vivo; this represents almost a quarter of this large group of natural products. It is also the parent compound of the secoiridoids. Many of the compounds derived from secologanin display a high degree of biological activity and are employed as pharmaceuticals, e.g., the dimeric indole alkaloid leurocristine (vincristine) which is used very successfully in the treatment of acute leukemia. A knowledge of the biosynthesis and biological reactions of secologanin provides a sound basis for the biosynthesis‐orientated classification of numerous natural products and the taxonomy of many plants. Secologanin and structurally related substances can be synthesized in a few steps by stereocontrolled photochemical and thermal cycloadditions. Its biomimetic reaction with amines and amino acids yields other natural products and compounds of pharmacological interest.

Studies in plant tissue culture: The synthesis and biosynthesis of indole alkaloids

Studies involving plant tissue cultures of Catharanthus roseus are described. Investigations concerning the propagation of cell lines of this plant for the purposes of producing indole alkaloids within the Corynanthé, Aspidosperma and Iboga families are presented. The utilization of such tissue culture systems for studies in biosyntheses and isolation of enzymes are also discussed.

Influence of phosphate on the formation of the indole alkaloids and phenolic compounds in cell suspension cultures of Catharanthus roseus I. Comparison of enzyme activities and product accumulation

In cell suspension cultures of Catharanthus roseus a rapid accumulation of secondary compounds (tryptamine, indole alkaloids, phenolics) was observed after transfer of the cells into special ‘induction’-media devoid of phosphate and other essential growth factors [11, 14]. The increase of product levels was suppressed in the presence of phosphate which was almost completely taken up from the medium and accumulated by the cells within 48 h after inoculation. The activities of tryptophan decarboxylase (TDC), the first enzyme in indole alkaloid biosynthesis, and of phenyl-alanine ammonia-lyase (PAL), the key enzyme of phenylpropanoid biosynthesis, were influenced differently by phosphate. Whereas the accumulation of phenolics and PAL activity were similarly inhibited by low concentration of phosphate, the medium-induced enhanced activity of TDC was not affected although the product pools were considerably reduced. Some consequences for the regulation of secondary metabolism will be discussed.

Biosynthesis of the Indole Alkaloids. Cell‐free Systems from Catharanthus roseus Plants

AbstractCell‐free systems from Catharanthus roseus plants are utilized for various studies relating to the biosynthesis of indole alkaloids. Tryptamine (5) and secologanin (6), two fundamental building units, are shown to be incorporated into the alkaloid vindoline (7). In another study, catharanthine (18) and vindoline (7) are utilized by this enzyme system and coupled to the important bisindole biointermediate 3′,4′‐anhydrovinblastineThe previously [20] used name for 17, 3′, 4′‐dehydrovinblastine, is incorrect. (17). The latter substance is, in turn, incorporated and converted to the natural alkaloids leurosine (8), Catharine (9) and vinblastine (10), thereby providing information about the biosynthesis of these complex molecules. High pressure liquid chromatography assay of the enzymic mixture sheds light on the enzymes involved in the coupling of 18 and 7.

Efficient Incorporation of 10-Hydroxygeraniol and 10-Hydroxynerol into Indole Alkaloids by a Cell Suspension Culture ofCatharanthus roseus*

A cell suspension culture of Catharanthus roseus was evaluated with regard to its potential usage in studies of early stage indole alkaloid biosynthesis. Employing this material, 1,1,7-trideutero-10-hydroxygeraniol and 1,1,7-trideutero-10-hydroxynerol were incorporated into the alkaloids ajmalicine and strictosidine lactam in approximate proportions of 50% and 80% respectively.

ChemInform Abstract: INDOLE ALKALOID BIOSYNTHESIS

Chemischer InformationsdienstVolume 12, Issue 38 Reviews ChemInform Abstract: INDOLE ALKALOID BIOSYNTHESIS A. I. SCOTT, A. I. SCOTTSearch for more papers by this authorS.-L. LEE, S.-L. LEESearch for more papers by this authorM. G. CULVER, M. G. CULVERSearch for more papers by this authorW. WAN, W. WANSearch for more papers by this authorT. HIRATA, T. HIRATASearch for more papers by this authorF. GUERITTE, F. GUERITTESearch for more papers by this authorR. L. BAXTER, R. L. BAXTERSearch for more papers by this authorH. + NORDLOEV, H. + NORDLOEVSearch for more papers by this authorC. A. DORSCHEL, C. A. DORSCHELSearch for more papers by this authorH. MIZUKAMI, H. MIZUKAMISearch for more papers by this authorN. E. MACKENZIE, N. E. MACKENZIESearch for more papers by this author A. I. SCOTT, A. I. SCOTTSearch for more papers by this authorS.-L. LEE, S.-L. LEESearch for more papers by this authorM. G. CULVER, M. G. CULVERSearch for more papers by this authorW. WAN, W. WANSearch for more papers by this authorT. HIRATA, T. HIRATASearch for more papers by this authorF. GUERITTE, F. GUERITTESearch for more papers by this authorR. L. BAXTER, R. L. BAXTERSearch for more papers by this authorH. + NORDLOEV, H. + NORDLOEVSearch for more papers by this authorC. A. DORSCHEL, C. A. DORSCHELSearch for more papers by this authorH. MIZUKAMI, H. MIZUKAMISearch for more papers by this authorN. E. MACKENZIE, N. E. MACKENZIESearch for more papers by this author First published: September 22, 1981 https://doi.org/10.1002/chin.198138369Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume12, Issue38September 22, 1981 RelatedInformation

Medium-Induced Formation of Indole Alkaloids and Concomitant Changes of Interrelated Enzyme Activities in Cell Suspension Cultures of Catharanthus roseus

Abstract Recently medium conditions have been developed which stimulate the formation of the indole alkaloid ajmalicine in cell suspension cultures of Catharanthus roseus [6]. When cells were subjected to these conditions the alkaloid accumulation was preceded by a 12-fold increase of the specific activity of tryptophan decarboxylase. The enzyme activity showed a maximum two days after the cell transfer into the induction medium and subsequently declined. In contrast the activity of strictosidine synthase, the enzyme condensing tryptamine and secologanin, was present over the entire measuring period at a constant level. The intracellular content of tryp­tamine and ajmalicine increased during a period of 6 days after cell transfer and reached a plateau after that time. A possible regulatory function of tryptophan decarboxylase in indole alkaloid biosynthesis is discussed.

Effects of bioregulators on indole alkaloid biosynthesis in Catharanthus roseus cell culture

Several carotenoid-inducers are effective in promoting indole alkaloid formation in Catharanthtus roseus cell culture. Among the five compounds tested, viz. 1,1-dimethylpiperidine, 2-diethylaminoethyl-3,4-dichlorophenylether, 2-diethylaminoethyl-2,4-dichlorophenylether, 2-diethylaminoethyl-β-naphthylether and 2-diethylaminoethyl-3,4-dimethylphenylether, 1,1-dimethylpiperidine, 2-diethylaminoethyl-2,4-dichlorophenylether and 2-diethylaminoethyl-β-naphthylether at 5 ppm concentration increased total alkaloid production by up to ca 20 % with concomitant increases in ajmalicine and catharanthine. Concentrations of 2-diethylaminoethyl-2,4-dichlorophenylether higher than 5 ppm caused growth inhibition and decrease in alkaloid synthesis.

Glucosidases involved in indole alkaloid biosynthesis of Catharanthus cell cultures

Glucosidases involved in indole alkaloid biosynthesis of Catharanthus cell cultures

Production of alkaloids and related substances by fungi. XV. On the mechanism of the formation of indole alkaloids in Penicillium roqueforti.

Studies on the biosynthesis of indole alkaloids in Penicillium roqueforti were carried out with the growing mycelia of a selected strain of the same mold by the use of DL-tryptophan-3-14C, DL-mevalonic acid-2-14C-lactone or L-methionine-methyl-14C as a precursor of ergoline alkaloids and DL-tryptophan-3-14C, DL-tryptophan-carboxy-14C, DL-mevalonic acid-2-14C-Iactone or L-histidine-ring-2-14C as a precursor of non-ergoline alkaloids. The results of these experiments seem to suggest that in the Penicillium mold employed there exist the following biosynthetic routes:_??_

ChemInform Abstract: ROLE OF ANHYDROVINBLASTINE IN THE BIOSYNTHESIS OF THE ANTITUMOR DIMERIC INDOLE ALKALOIDS

Chemischer InformationsdienstVolume 9, Issue 51 Natural Products ChemInform Abstract: ROLE OF ANHYDROVINBLASTINE IN THE BIOSYNTHESIS OF THE ANTITUMOR DIMERIC INDOLE ALKALOIDS A. I. SCOTT, A. I. SCOTTSearch for more papers by this authorF. GUERITTE, F. GUERITTESearch for more papers by this authorS.-L. LEE, S.-L. LEESearch for more papers by this author A. I. SCOTT, A. I. SCOTTSearch for more papers by this authorF. GUERITTE, F. GUERITTESearch for more papers by this authorS.-L. LEE, S.-L. LEESearch for more papers by this author First published: December 19, 1978 https://doi.org/10.1002/chin.197851352Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume9, Issue51December 19, 1978 RelatedInformation

The Biosynthesis of the Ipecac Alkaloids and of Ipecoside and Alangiside

The synthesis of (1–3H, 3–14C)–(1α)–desacetylisoipecoside and –(1β)–desacetylipecoside is described. Feeding experiments with the pure epimers showed that in contrast to previous assumptions, desacetylisoipecoside is the true precursor for the ipecac alkaloids (cephaeline and emetine) in both Cephaelis and Alangium. The 1β epimer, desacetylipecoside, is the precursor only of the alkaloidal glucosides, ipecoside and alangiside, both of which posses the β–configuration. A biosynthetic scheme for the formation of these compounds is proposed and the difference between this pathway and monoterpenoid indole alkaloid biosynthesis is discussed.

Tissue cultivation of rose-colored periwinkle. Biosynthesis of indole alkaloids

The material for the study was the callus tissue of the rose-colored periwinkle stalk (2 year old). The experiments in the growth of the suspension culture were carried out in 80-ml culture vessels and in 5-1iter flasks containing i0 and 3 ml of the medium, respectively. The initial biomass content in the vessels and the flask was 30 g/liter. Cultivation was performed on rollers at a rate of 2 rpm with continuous magnetic stirring (i00 rpm) and sterile air introduction at a rate of 0.2 liters/min.

Synthetic Studies of anti-Leukaemic Alkaloids, IX* / Some Aspects of the Chemistry of C atliar anthine

Abstract Vinblastine and Vincristine are binary indole-indoline alkaloids occurring in traces in the leaves of Vinca rosea. They are among the most powerful chemotherapeutic agents available to man for the treatment of a variety of cancers. Their high cost and complexity of structure has attracted the attention of many eminent chemists towards their synthesis. The first synthesis of both these anti-tumour alkaloids was reported by us last year [7] starting from two major alkaloids, catharanthine and vindo-line, which co-occur in the same plant. Some aspects of the chemistry of catharanthine are now presented including a novel one-step de-carbomethoxylation reaction with H2S in glacial acetic acid and a reversible isomerization of catharanthine with sodium borohydride. A study of the life-time of catharanthine in hot glacial acetic acid substantiates the earlier work of the Anglo-French group on the biosynthesis of indole alkaloids.

Biosynthesis of the dimeric indole alkaloids. II. Catharanthine as a precursor of vincaleukoblastine.

Biosynthesis of the dimeric indole alkaloids. II. Catharanthine as a precursor of vincaleukoblastine.

The basic glucosides related to the biosynthesis of indole and ipecac alkaloids

The basic glucosides related to the biosynthesis of indole and ipecac alkaloids

Indole alkaloid biosynthesis: An investigation into leucine as a possible precursor of the monoterpene portion of vindoline

Because of the nonspecific incorporation of acetate into the monoterpenoid portion of the indole alkaloids, the amino acid leucine has been investigated as an alternative precursor. Incorporations of leucine into the alkaloids vindoline and catharanthine in Vinca rosea are found to be 0.07 and 0.02%, respectively, levels comparable with those of acetate. An equation is developed to calculate the quantity of [ 13C]leucine needed to be fed in order to obtain alkaloids with sufficient 13C enrichment to be analysed by 13C nmr spectroscopy. This equation assumes that percentage incorporations do not decrease with increasing quantities of leucine fed, an assumption found to be true. [2- 13C]Leucine was synthesized from [2- 13C]acetic acid in an eight-step procedure in 11.5% overall yield, and fed to Vinca rosea plants. Incorporations into vindoline obtained using both 14C and 13C were in reasonable agreement, and the activity was found to be spread over seven carbon atoms, none of which corresponded to the two atoms at which activity was expected. It is concluded that the leucine → mevalonate → monoterpene route does not operate in indole alkaloid biosynthesis, leaving open the question of the origin of the monoterpene portion of the alkaloids. An attempt to confirm these results by degradation of 14C-labelled alkaloids was unsuccessful, vindoline proving to be unexpectedly resistant to oxidation.

Subcellular localization of a cytochrome P-450-dependent monogenase in vesicles of the higher plant Catharanthus roseus.

The intracellular location of a cytochrome P-450-dependent monoterpene hydroxylase from the higher plant, Catharanthus roseus, has been investigated. By differential and sucrose density gradient centrifugation, utilizing marker enzymes and electron microscopy, the monooxygenase was demonstrated to be associated with vesicles having a membrane thickness of 40-60 nm. The vesicles could be distinguished from endoplasmic reticulum, Golgi apparatus, mitochondria, and plasma membrane and were found in light membrane fractions containing provacuoles. Most definitive results were obtained when seedlings were ground in the presence of sand and in a medium containing sorbitol. Upon subjection of the 20,000-g pellet preparation to linear sucrose density gradient centrifugation, a threefold enrichment in hydroxylase activity was afforded in a yellow band having vesicles varying in size from 0.1 to 0.8 mum in diam and having a density of 1.09 to 1.10 g/cm3. Since the monooxygenase has been implicated in indole alkaloid biosynthesis in this plant, the data suggest the compartmentalization of at least a part of this pathway.