Showing papers on "Indole alkaloid published in 2007"
TL;DR: This review mainly summarizes the progress made on biochemical engineering aspects of C. roseus cell cultures in bioreactors in the past decades and metabolic engineering of indole alkaloids production in recent years and attempts to highlight new strategies and technologies to improve alkaloid production and bioreactor performance.
Abstract: Catharanthus roseus plants produce many pharmaceutically important indole alkaloids, of which the bisindole alkaloids vinblastine and vincristine are antineoplastic medicines and the monoindole alkaloids ajmalicine and serpentine are antihypertension drugs. C. roseus cell cultures have been studied for producing these medicines or precursors catharanthine and vindoline for almost four decades but so far without a commercially successful process due to biological and technological limitations. The research thus focused on the one hand on engineering the bioreactor process on the other engineering the cell factory itself. This review mainly summarizes the progress made on biochemical engineering aspects of C. roseus cell cultures in bioreactors in the past decades and metabolic engineering of indole alkaloid production in recent years. The paper also attempts to highlight new strategies and technologies to improve alkaloid production and bioreactor performance. Perspectives of metabolic engineering to create new cell lines for large-scale production of indole alkaloids in bioreactors and effective combination of these up- and down-stream processing are presented.
133 citations
TL;DR: Detailed three-dimensional information is reported describing both native SG and the complex of its inactive mutant Glu207Gln with the substrate strictosidine, thus providing a structural characterization of substrate binding and identifying the amino acids that occupy the active site surface of the enzyme.
Abstract: Strictosidine β-d-glucosidase (SG) follows strictosidine synthase (STR1) in the production of the reactive intermediate required for the formation of the large family of monoterpenoid indole alkaloids in plants. This family is composed of ∼2000 structurally diverse compounds. SG plays an important role in the plant cell by activating the glucoside strictosidine and allowing it to enter the multiple indole alkaloid pathways. Here, we report detailed three-dimensional information describing both native SG and the complex of its inactive mutant Glu207Gln with the substrate strictosidine, thus providing a structural characterization of substrate binding and identifying the amino acids that occupy the active site surface of the enzyme. Structural analysis and site-directed mutagenesis experiments demonstrate the essential role of Glu-207, Glu-416, His-161, and Trp-388 in catalysis. Comparison of the catalytic pocket of SG with that of other plant glucosidases demonstrates the structural importance of Trp-388. Compared with all other glucosidases of plant, bacterial, and archaeal origin, SG9s residue Trp-388 is present in a unique structural conformation that is specific to the SG enzyme. In addition to STR1 and vinorine synthase, SG represents the third structural example of enzymes participating in the biosynthetic pathway of the Rauvolfia alkaloid ajmaline. The data presented here will contribute to deciphering the structure and reaction mechanism of other higher plant glucosidases.
91 citations
TL;DR: It is demonstrated that with a different expression system and screening method it is possible to rapidly identify strictosidine synthase variants that accept tryptamine analogs not turned over by the wild-type enzyme.
86 citations
TL;DR: Indole-3-carbaldehyde and 5-deoxyhyrtiosine A are reporterd for the first time in the genus Hertios, in addition to other indole alkaloids and three scalarane sesterterpenes from the Red Sea sponge Hertios erectus, for their cytotoxic and antimicrobial activities.
Abstract: Indole-3-carbaldehyde and 5-deoxyhyrtiosine A are reporterd for the first time in the genus Hertios, in addition to other indole alkaloids and three scalarane sesterterpenes, from the Red Sea sponge Hertios erectus. The isolated compounds were tested for their cytotoxic and antimicrobial activities.
41 citations
TL;DR: In this article, a 10b-methyl- or 10bhydroxy-1,2,4,5,10b,10c-hexahydropyrrolo[1,9a,9]indole skeleton was obtained by highly stereoselective electrophile addition-cyclization reactions of a tryptophan-derived α-amino nitriles.
13 citations
TL;DR: The synthesis of new indole alkaloid analogues, containing a 1,2,4,5,10b,10c-hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole skeleton, via highly stereoselective novel domino cyclative halogenation or prenylation reactions of tryptophan-derived alpha-amino nitriles is described
Abstract: The synthesis of new indole alkaloid analogues, containing a 1,2,4,5,1 Ob, 1 Oc-hexahydropyrrolo[ 1 ',2',3': 1,9a,9]imidazo-[1,2-a]indole skeleton, via highly stereoselective novel domino cyclative halogenation or prenylation reactions of tryptophan-derived α-amino nitriles, is described.
12 citations
TL;DR: In this article, a yohimbane-type indole alkaloid, ourouparine, was found in Gelsemium sempervirens and its structure was elucidated by spectroscopic analysis and total synthesis.
Abstract: A yohimbane-type indole alkaloid, ourouparine, was found in Gelsemium sempervirens, and its structure was elucidated by spectroscopic analysis and total synthesis.
10 citations
TL;DR: A useful method is developed, based on enzyme-assisted synthesis, to produce strictosidine, a key intermediate in the biosynthesis of the terpenoid indole alkaloid (T1A) pathway.
Abstract: Strictosidine is a key intermediate in the biosynthesis of the terpenoid indole alkaloid (T1A) pathway. It results from a condensation reaction, catalyzed by strictosidine synthase (STR), between tryptamine and secologanin. We have now developed a useful method, based on enzyme-assisted synthesis, to produce strictosidine. Our procedure utilizes leaf extracts from Japanese honeysuckleLonicera japonica Thunb. as a secologanin source. In these experiments, an enzyme extract was prepared from transgenic yeastSaccharomyces cerevisiae that expresses theCatharanthus roseus STR (CrSTR) coding region. Strictosidine was then isolated with a 38% yield based on the initial amount of tryptamine in the enzymatic reaction.
6 citations
Journal Article•
TL;DR: An indole alkaloid has been isolated from the culture extract of one endophyte derived from the root of Caragana sinica(Buc'hoz) Rehd and the crystal structure of Neoechinulin A was determined by single-crystal X-ray diffraction analysis for the first time.
Abstract: An indole alkaloid has been isolated from the culture extract of one endophyte derived from the root of Caragana sinica(Buc'hoz) Rehd.Its structure has been identified by spectral methods as Neoechinulin A.Besides,the crystal of the compound was acquired,and the crystal structure of Neoechinulin A was determined by single-crystal X-ray diffraction analysis for the first time.
3 citations
01 Jan 2007
TL;DR: In this paper, three glycosides were isolated from the branch-bark of Davidia involucrata NMR and MS methods were used to elucidate their chemical structures The three compounds were determined as one quinoline alkaloid glycoside-pumiloside (1) and two indole alk aloid glycoides-vincosamide (2),strictosidinic acid (3).
Abstract: Three glycosides were isolated from the branch-bark of Davidia involucrata NMR and MS methods were used to elucidate their chemical structures The three compounds were determined as one quinoline alkaloid glycoside-pumiloside (1) and two indole alkaloid glycosides-vincosamide (2),strictosidinic acid (3) All these compounds were isolated from Dinvolucrata for the first time
2 citations
Dissertation•
09 Jun 2007
TL;DR: A chemical investigation of Aspidosperma excelsum yielded excelsinidine (1), a quaternary indole alkaloid possessing an unusual 1-azoniatricyclo[4.3.0]undecane moiety, along with the known compou...
Abstract: A chemical investigation of Aspidosperma excelsum yielded excelsinidine (1), a quaternary indole alkaloid possessing an unusual 1-azoniatricyclo[4.3.3.0]undecane moiety, along with the known compou...
TL;DR: An efficient use of RCM leading to a convenient synthesis of a pentacyclic indole alkaloid was described in this article, where the RCM was used to obtain the indole acid.
Abstract: An efficient utilisation of RCM leading to a convenient synthesis of a pentacyclic indole alkaloid is described.
TL;DR: The exocyclic analogue of the indole alkaloid isolated from the marine sponge Halichondria melanodocia has been prepared via olefination of a phosphonoester derived from 3-(2-bromoacyl)indole as mentioned in this paper.
Abstract: The exocyclic analogue of the indole alkaloid isolated from the marine sponge Halichondria melanodocia has been prepared via olefination of a phosphonoester derived from 3-(2-bromoacyl)indole. The formation of an unexpected indolylazepine is also discussed.