ergoline and chanoclavine

All plants harbor many microbial species including bacteria and fungi in their tissues. The interactions between the plant and these microbes could be symbiotic, mutualistic, parasitic or commensalistic. Mutualistic microorganisms are endophytic in nature and are known to play a role in plant growth, development and fitness. Endophytes display complex diversity depending upon the agro-climatic conditions and this diversity could be exploited for crop improvement and sustainable agriculture. Plant-endophyte partnerships are highly specific, several genetic and molecular cascades play a key role in colonization of endophytes in host plants leading to rapid changes in host and endophyte metabolism. This results in the accumulation of secondary metabolites, which play an important role in plant defense against biotic and abiotic stress conditions. Alkaloids are one of the important class of metabolites produced by Epichloë genus and other related classes of endophytes and confer protection against insect and mammalian herbivory. In this context, this review discusses the evolutionary aspects of the Epichloë genus along with key molecular mechanisms determining the lifestyle of Epichloë endophytes in host system. Novel hypothesis is proposed to outline the initial cellular signaling events during colonization of Epichloë in cool season grasses. Complex clustering of alkaloid biosynthetic genes and molecular mechanisms involved in the production of alkaloids have been elaborated in detail. The natural defense and advantages of the endophyte derived metabolites have also been extensively discussed. Finally, this review highlights the importance of endophyte-arbitrated plant immunity to develop novel approaches for eco-friendly agriculture.

Topics: Alkaloids; Aspergillus; Calcineurin; Endophytes; Epichloe; Ergolines; Ergot Alkaloids; Evolution, Molecular; Fungal Proteins; Indole Alkaloids; Lysergic Acid; Multigene Family; NADPH Oxidases; Plant Immunity; Poaceae; Protein Kinases; Reactive Oxygen Species; Stress, Physiological; Symbiosis; Transcriptome

Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes.

Topics: Ascomycota; Aspergillus; Biosynthetic Pathways; Claviceps; Ergolines; Ergot Alkaloids; Lysergic Acid; Multigene Family; Penicillium

Irritable bowel syndrome (IBS) is a chronic disease that causes abdominal pain and an imbalance of defecation patterns due to gastrointestinal dysfunction. The cause of IBS remains unclear, but intestinal-brain axis problems and neurotransmitters have been suggested as factors. In this study, chanoclavine, which has a ring structure similar to 5-hydroxytryptamine (5-HT), showed an interaction with the 5-HT

Topics: Dose-Response Relationship, Drug; Ergolines; Ergonovine; Humans; Molecular Conformation; Molecular Docking Simulation; Receptors, Serotonin, 5-HT3; Serotonin; Signal Transduction

The emergence of multi drug resistance (MDR) in Gram-negative bacteria (GNB) and lack of novel classes of antibacterial agents have raised an immediate need to identify antibacterial agents, which can reverse the phenomenon of MDR. The purpose of present study was to evaluate synergy potential and understanding the drug resistance reversal mechanism of chanoclavine isolated from Ipomoea muricata against the multi-drug-resistant clinical isolate of Escherichia coli (MDREC). Although chanoclavine did not show antibacterial activity of its own, but in combination, it could reduce the minimum inhibitory concentration (MIC) of tetracycline (TET) up to 16-folds. Chanoclavine was found to inhibit the efflux pumps which seem to be ATPase-dependent. In real-time expression analysis, chanoclavine showed down-regulation of different efflux pump genes and decreased the mutation prevention concentration of tetracycline. Further, in silico docking studies revealed significant binding affinity of chanoclavine with different proteins known to be involved in drug resistance. In in silico ADME/toxicity studies, chanoclavine was found safe with good intestinal absorption, aqueous solubility, medium blood-brain barrier (BBB), no CYP 2D6 inhibition, no hepatotoxicity, no skin irritancy, and non-mutagenic indicating towards drug likeliness of this molecule. Based on these observations, it is hypothesized that chanoclavine might be inhibiting the efflux of tetracycline from MDREC and thus enabling the more availability of tetracycline inside the cell for its action.

Topics: Adenosine Triphosphatases; Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Ergolines; Escherichia coli; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Mutation; Structure-Activity Relationship; Tetracycline

Topics: Animals; Endophytes; Ergolines; Female; Insecticides; Lethal Dose 50; Male; Mice; Pest Control, Biological; Secondary Metabolism

Ergot alkaloids are specialized fungal metabolites with potent biological activities. They are encoded by well-characterized gene clusters in the genomes of producing fungi.

Topics: Chromatography, High Pressure Liquid; Ergolines; Ergot Alkaloids; Fungal Proteins; Genome, Fungal; Mass Spectrometry; Penicillium

An efficient and direct route to ergot alkaloid (-)-chanoclavine I (3) is described using the inexpensive compound (2R)-(+)-phenyloxirane (15) as a chiral pool in 13 steps with 17% overall yield. Key features of the synthesis include a palladium-catalyzed intramolecular aminoalkynylation of terminal olefin and a rhodium-catalyzed intramolecular [3 + 2] annulation. An oxygen-substituted ergoline derivative (-)-25 was also achieved by using the same strategy.

Topics: Catalysis; Ergolines; Molecular Structure; Oxygen; Rhodium

Epichloid endophytes are well known symbionts of many cool-season grasses that may alleviate environmental stresses for their hosts. For example, endophytes produce alkaloid compounds that may be toxic to invertebrate or vertebrate herbivores. Achnatherum robustum, commonly called sleepygrass, was aptly named due to the presence of an endophyte that causes toxic effects to livestock and wildlife. Variation in alkaloid production observed in two A. robustum populations located near Weed and Cloudcroft in the Lincoln National Forest, New Mexico, suggests two different endophyte species are present in these populations. Genetic analyses of endophyte-infected samples revealed major differences in the endophyte alkaloid genetic profiles from the two populations, which were supported with chemical analyses. The endophyte present in the Weed population was shown to produce chanoclavine I, paspaline, and terpendoles, so thus resembles the previously described Epichloë funkii. The endophyte present in the Cloudcroft population produces chanoclavineI, ergonovine, lysergic acid amide, and paspaline, and is an undescribed endophyte species. We observed very low survival rates for aphids feeding on plants infected with the Cloudcroft endophyte, while aphid survival was better on endophyte infected plants in the Weed population. This observation led to the hypothesis that the alkaloid ergonovine is responsible for aphid mortality. Direct testing of aphid survival on oat leaves supplemented with ergonovine provided supporting evidence for this hypothesis. The results of this study suggest that alkaloids produced by the Cloudcroft endophyte, specifically ergonovine, have insecticidal properties.

Topics: Alkaloids; Animals; Aphids; Endophytes; Epichloe; Ergolines; Ergonovine; Ergot Alkaloids; Genetic Variation; Herbivory; Indoles; Insecticides; Lysergic Acid Diethylamide; New Mexico; Poaceae

Nowadays psychoactive plants marketed as "legal highs" or "herbal highs" increase in popularity. One popular "legal high" are the seeds of the Hawaiian baby woodrose Argyreia nervosa (Synonym: Argyreia speciosa, Convolvolus speciosus). At present there exists no study on A. nervosa seeds or products, which are used by consumers. The quality of commercial available A. nervosa seeds or products is completely unknown. In the present study, a commercial available seed collection (five seeds labeled "flash of inspiration", FOI) was analyzed for ergot alkaloids together with an A. nervosa product (two preparations in capsule form, "druids fantasy", DF). For this purpose high performance liquid chromatography high resolution tandem mass spectrometry (HPLC-HRMS/MS) technique was employed. Besides the major ingredients such as lysergic acid amide (LSA) and ergometrine the well known A. nervosa compounds lysergol/elymoclavine/setoclavine, chanoclavine and the respective stereoisomers were detected in DF, while only LSA and ergometrine could be found in FOI. In addition, in DF lysergic acid was found, which has not been reported yet as ingredient of A. nervosa. In both products, DF as well as in FOI, LSA/LSA-isomers were dominant with 83-84% followed by ergometrine/ergometrinine with 10-17%. Therefore, LSA, followed by ergometrine/ergometrinine, could be confirmed to be the main ergot alkaloids present in A. nervosa seeds/products whereas the other ergot alkaloids seemed to be of minor importance (less than 6.1% in DF). The total ergot alkaloid amounts varied considerably between DF and FOI by a factor of 8.6 as well as the LSA concentration ranging from 3 μg (lowest amount in one FOI seed) to approximately 34 μg (highest amount in one DF capsule). Among the FOI seeds, the LSA concentration varied from approximately 3-15 μg per seed. Thus, the quality/potency of seeds/preparations depends on the amount of ergot alkaloids and the intensity of an expected trip is totally unpredictable.

Topics: Alkaloids; Chromatography, Liquid; Convolvulus; Ergolines; Ergonovine; Humans; Indoles; Lysergic Acid Diethylamide; Molecular Structure; Psychotropic Drugs; Seeds; Tandem Mass Spectrometry

Ergot alkaloids are a group of highly bioactive molecules produced by a number of filamentous fungi. These compounds have been intensely studied for decades, mainly due to their deleterious effects in contaminated food and feeds, but also for their beneficial pharmaceutical and agricultural applications. Biosynthesis of ergot alkaloids goes via the common intermediate chanoclavine-I, and studies of the key enzymes, EasE and EasC, involved in chanoclavine-I formation, have relied on gene complementation in fungi, whereas further characterization has been hampered by difficulties of poor EasE protein expression. In order to facilitate the study of ergot alkaloids, and eventually move towards commercial production, the early steps of the biosynthetic pathway were reconstituted in the unicellular yeast Saccharomyces cerevisiae.. The genomic sequence from an ergot alkaloid producer, Aspergillus japonicus, was used to predict the protein encoding sequences of the early ergot alkaloid pathway genes. These were cloned and expressed in yeast, resulting in de novo production of the common intermediate chanoclavine-I. This allowed further characterization of EasE and EasC, and we were able to demonstrate how the N-terminal ER targeting signal of EasE is crucial for activity in yeast. A putative, peroxisomal targeting signal found in EasC was shown to be nonessential. Overexpression of host genes pdi1 or ero1, associated with disulphide bond formation and the ER protein folding machinery, was shown to increase chanoclavine-I production in yeast. This was also the case when overexpressing host fad1, known to be involved in co-factor generation.. A thorough understanding of the enzymatic steps involved in ergot alkaloid formation is essential for commercial production and exploitation of this potent compound class. We show here that EasE and EasC are both necessary and sufficient for the production of chanoclavine-I in yeast, and we provide important new information about the involvement of ER and protein folding for proper functional expression of EasE. Moreover, by reconstructing the chanoclavine-I biosynthetic pathway in yeast we demonstrate the advantage and potential of this host, not only as a convenient model system, but also as an alternative cell factory for ergot alkaloid production.

Topics: Aspergillus; Biosynthetic Pathways; Ergolines; Ergot Alkaloids; Fungal Proteins; Genes, Fungal; Genetic Engineering; Open Reading Frames; Peroxisomes; Protein Sorting Signals; Saccharomyces cerevisiae; Tryptophan

A rapid, simple, sensitive, gradient and reproducible, reverse-phase high-performance liquid chromatographic method was developed for the quantitative estimation of bioactive alkaloids, lysergol and chanoclavine in the seeds of Ipomoea muricata. The clavine alkaloid, lysergol, is a bioenhancer for the drugs and nutrients. The samples were analyzed by reverse-phase chromatography on a Waters spherisorb ODS2 column (250 × 4.6 mm, i.d., 10 µm) using binary gradient elution with acetonitrile and 0.01 m phosphate buffer (NaH₂PO₄) containing 0.1% glacial acetic acid at a flow rate of 0.8 mL/min, a column temperature of 25 °C and UV detection at λ 254 nm. The limits of detection (LOD) and quantitation (LOQ) were 0.035 and 0.106 µg/mL for lysergol and 0.039 and 0.118 µg/mL for chanoclavine, respectively. Standard curves were linear in the range of 2-10 µg/mL (r > 99) for both analytes. Good results were achieved with respect to repeatability (RSD < 2%) and recovery (99.20-102.0). The method was validated for linearity, accuracy repeatability, LOQ and LOD. The method is simple, accurate and precise, and may be recommended for routine quality control analysis of I. muricata seed extracts containing these two clavine alkaloids (1, 2) as bioactive principles of the herb.

Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Ergolines; Ipomoea; Least-Squares Analysis; Reproducibility of Results; Seeds; Sensitivity and Specificity

Genes required for ergot alkaloid biosynthesis are clustered in the genomes of several fungi. Several conserved ergot cluster genes have been hypothesized, and in some cases demonstrated, to encode early steps of the pathway shared among fungi that ultimately make different ergot alkaloid end products. The deduced amino acid sequence of one of these conserved genes (easC) indicates a catalase as the product, but a role for a catalase in the ergot alkaloid pathway has not been established. We disrupted easC of Aspergillus fumigatus by homologous recombination with a truncated copy of that gene. The resulting mutant (ΔeasC) failed to produce the ergot alkaloids typically observed in A. fumigatus, including chanoclavine-I, festuclavine, and fumigaclavines B, A, and C. The ΔeasC mutant instead accumulated N-methyl-4-dimethylallyltryptophan (N-Me-DMAT), an intermediate recently shown to accumulate in Claviceps purpurea strains mutated at ccsA (called easE in A. fumigatus) (Lorenz et al. Appl Environ Microbiol 76:1822-1830, 2010). A ΔeasE disruption mutant of A. fumigatus also failed to accumulate chanoclavine-I and downstream ergot alkaloids and, instead, accumulated N-Me-DMAT. Feeding chanoclavine-I to the ΔeasC mutant restored ergot alkaloid production. Complementation of either ΔeasC or ΔeasE mutants with the respective wild-type allele also restored ergot alkaloid production. The easC gene was expressed in Escherichia coli, and the protein product displayed in vitro catalase activity with H(2)O(2) but did not act, in isolation, on N-Me-DMAT as substrate. The data indicate that the products of both easC (catalase) and easE (FAD-dependent oxidoreductase) are required for conversion of N-Me-DMAT to chanoclavine-I.

Topics: Allyl Compounds; Aspergillus fumigatus; Catalase; Claviceps; Cloning, Molecular; Ergolines; Ergonovine; Ergot Alkaloids; Escherichia coli; Fungal Proteins; Hydrogen Peroxide; Indole Alkaloids; Multigene Family; Oxidoreductases; Recombinant Proteins; Recombination, Genetic; Sequence Deletion; Tryptophan

A previous study showed that together with the festuclavine synthase FgaFS, the old yellow enzyme FgaOx3 from Aspergillus fumigatus catalyzed the conversion of chanoclavine-I aldehyde to festuclavine in the biosynthesis of ergot alkaloids. In the absence of FgaFS, a mixture containing two compounds with a ratio of 7:3 was detected in the enzyme assay of FgaOx3. NMR experiments including (DQF)-COSY, HSQC, HMBC and NOESY identified their structures as E/Z isomers of N-methyl-N-[(5R,10R)-10-(2-oxo-propyl)-2,4,5,10-tetrahydrobenzo[cd]indol-5-yl]formamide and proved the migration of the formyl group at C-8 in chanoclavine I-aldehyde to N-6 in the identified products.

Topics: Aldehydes; Aspergillus fumigatus; Biocatalysis; Ergolines; Magnetic Resonance Spectroscopy; Molecular Structure; NADPH Dehydrogenase; Reference Standards; Stereoisomerism

Ergot alkaloids are toxins and important pharmaceuticals which are produced biotechnologically on an industrial scale. A putative gene fgaDH has been identified in the biosynthetic gene cluster of fumigaclavine C, an ergot alkaloid of the clavine-type. The deduced gene product FgaDH comprises 261 amino acids with a molecular mass of about 27.8 kDa and contains the conserved motifs of classical short-chain dehydrogenases/reductases (SDRs), but shares no worth mentioning sequence similarity with SDRs and other known proteins. The coding region of fgaDH consisting of two exons was amplified by PCR from a cDNA library of Aspergillus fumigatus, cloned into pQE60 and overexpressed in E. coli. The soluble tetrameric His(6)-FgaDH was purified to apparent homogeneity and characterized biochemically. It has been shown that FgaDH catalyzes the oxidation of chanoclavine-I in the presence of NAD(+) resulting in the formation of chanoclavine-I aldehyde, which was unequivocally identified by NMR and MS analyzes. Therefore, FgaDH functions as a chanoclavine-I dehydrogenase and represents a new group of short-chain dehydrogenases. K (M) values for chanoclavine-I and NAD(+) were determined at 0.27 and 1.1 mM, respectively. The turnover number was 0.38 s(-1).

Topics: Alcohol Dehydrogenase; Aspergillus fumigatus; Chromatography, High Pressure Liquid; Ergolines; Ergot Alkaloids; Fungal Proteins; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Sequence Data; Molecular Structure; NAD; Polymerase Chain Reaction

Ergot alkaloids, secondary metabolites produced by filamentous fungi, elicit a diverse array of pharmacological effects. The biosynthesis of this class of natural products has not been fully elucidated. Here we demonstrate that a homologue of Old Yellow Enzyme encoded in the Aspergillus fumigatus ergot gene cluster catalyzes reduction of the alpha,beta unsaturated alkene of chanoclavine-I aldehyde 3. This reduction, which yields dihydrochanoclavine aldehyde, facilitates an intramolecular reaction between a secondary amine and aldehyde to form the D ring of the ergot alkaloid structural framework.

Topics: Aldehydes; Aspergillus fumigatus; Biocatalysis; Biological Products; Ergolines; Ergot Alkaloids; Multigene Family; NADPH Dehydrogenase; Oxidation-Reduction; Sequence Homology, Amino Acid

Ergot alkaloids are indole-derived secondary metabolites synthesized by the phytopathogenic ascomycete Claviceps purpurea. In wild-type strains, they are exclusively produced in the sclerotium, a hibernation structure; for biotechnological applications, submerse production strains have been generated by mutagenesis. It was shown previously that the enzymes specific for alkaloid biosynthesis are encoded by a gene cluster of 68.5 kb. This ergot alkaloid cluster consists of 14 genes coregulated and expressed under alkaloid-producing conditions. Although the role of some of the cluster genes in alkaloid biosynthesis could be confirmed by a targeted knockout approach, further functional analyses are needed, especially concerning the early pathway-specific steps up to the production of clavine alkaloids. Therefore, the gene ccsA, originally named easE and preliminarily annotated as coding for a flavin adenine dinucleotide-containing oxidoreductase, was deleted in the C. purpurea strain P1, which is able to synthesize ergot alkaloids in axenic culture. Five independent knockout mutants were analyzed with regard to alkaloid-producing capability. Thin-layer chromatography (TLC), ultrapressure liquid chromatography (UPLC), and mass spectrometry (MS) analyses revealed accumulation of N-methyl-dimethylallyltryptophan (Me-DMAT) and traces of dimethylallyltryptophan (DMAT), the first pathway-specific intermediate. Since other alkaloid intermediates could not be detected, we conclude that deletion of ccsA led to a block in alkaloid biosynthesis beyond Me-DMAT formation. Complementation with a ccsA/gfp fusion construct restored alkaloid biosynthesis. These data indicate that ccsA encodes the chanoclavine I synthase or a component thereof catalyzing the conversion of N-methyl-dimethylallyltryptophan to chanoclavine I.

Topics: Biosynthetic Pathways; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Claviceps; Coenzymes; Ergolines; Flavin-Adenine Dinucleotide; Fungal Proteins; Gene Deletion; Genetic Complementation Test; Mass Spectrometry; Models, Biological; Oxidoreductases; Tryptophan

Ergot alkaloids are toxins and important pharmaceuticals which are produced biotechnologically on an industrial scale. A putative gene fgaFS has been identified in the biosynthetic gene cluster of fumigaclavine C, an ergot alkaloid of the clavine-type. The deduced gene product FgaFS comprises 290 amino acids with a molecular mass of about 32.1 kDa. The coding region of fgaFS consisting of three exons was amplified by PCR from a cDNA library of Aspergillus fumigatus, cloned into pQE70 and overexpressed in E. coli. The soluble monomeric His(6)-FgaFS was purified by affinity chromatography and used for enzyme assays. It has been shown that FgaFS is responsible for the conversion of chanoclavine-I aldehyde to festuclavine in the presence of the old yellow enzyme FgaOx3. The structure of festuclavine including the stereochemistry was unequivocally elucidated by NMR and MS analyses. Festuclavine formation was only observed when chanoclavine-I aldehyde was incubated with FgaOx3 and FgaFS simultaneously or as a tandem-reaction with a sequence of FgaOx3 before FgaFS. In the absence of FgaFS, two shunt products were formed and did not serve as substrates for FgaFS reaction.

Topics: Aldehydes; Aspergillus fumigatus; Cloning, Molecular; Ergolines; Ergot Alkaloids; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Multigene Family; NADPH Dehydrogenase; Sequence Analysis, DNA; Stereoisomerism

The abilities of tricyclic ergot alkaloids, chanoclavine-I and its analogues, and bromocriptine to stimulate dopamine receptors in the brain were investigated. Receptor binding of 3H-spiperone has shown that bromocriptine exhibits clear affinity for this compound. The order of displacement potencies was bromocriptine much greater than ergometrine, KSU-1415 greater than chanoclavine-I, KSU-1118, KSU-1791. In the striatum of mice treated with an amino acid decarboxylase inhibitor, gamma-butyrolactone-induced DOPA accumulation was markedly inhibited by bromocriptine and KSU-1415, but not inhibited by chanoclavine-I. In mice with unilateral striatal 6-hydroxydopamine lesions, bromocriptine and KSU-1415 produced a long-lasting contralateral rotation that was suppressed by prior treatment with (+/-)-sulpiride. These results suggest that a tricyclic ergot alkaloid of the chanoclavine type stimulates D-2 receptors in the brain.

Topics: 4-Butyrolactone; Animals; Binding, Competitive; Brain; Catechols; Corpus Striatum; Dihydroxyphenylalanine; Ergolines; Ergot Alkaloids; In Vitro Techniques; Male; Mice; Rats; Rats, Inbred Strains; Receptors, Dopamine; Rotation; Spiperone; Stereotyped Behavior; Time Factors

In submerged Claviceps cultures the activity of hydroxymethylglutaryl-CoA reductase preceded the increase of alkaloid production and of sterol content. During the first alkaloid phase, cell mevalonate was involved in the biosynthesis of both alkaloids and steroids. In the second production phase, it was predominantly used for alkaloid synthesis. Hydroxymethylglutaryl-CoA reductase appears to be a suitable target for physiological manipulation to increase clavine alkaloid yields.

Topics: Claviceps; Ergolines; Ergot Alkaloids; Hydroxymethylglutaryl CoA Reductases; Sterols

L-Tryptophan did not exert any influence on peptide alkaloid formation in an ergotamine and in an ergosine-accumulating C. purpurea strain. A different picture was observed in a series of related C. purpurea strains. Tryptophan showed a slight stimulatory effect on the ergotoxine producer Pepty 695/S. A blocked mutant of it, designated as Pepty 695/ch which was able to accumulate secoclavines gave similar results. In a high-yielding elymoclavine strain Pepty 695/e, the progeny of the former one, tryptophan up to a concentration of 25 mM stimulated remarkably clavine biosynthesis. Furthermore, tryptophan could overcome the block of synthesis by inorganic phosphate. Increased specific activities of chanoclavine cyclase but not DMAT synthetase were observed in cultures of strain Pepty 695/e supplemented with tryptophan. 5-Methyltryptophan and bioisosteres of tryptophan were ineffective in alkaloid stimulation. These results are compared with those obtained with the grass ergot strain SD 58 and discussed with the relation to other induction phenomena.

Topics: Chemical Phenomena; Chemistry; Claviceps; Culture Media; Ergolines; Ergot Alkaloids; Mutation; Phosphates; Stereoisomerism; Tryptophan

Topics: Claviceps; Cyclization; Deuterium; Ergolines; Ergot Alkaloids; Isomerism; Structure-Activity Relationship; Tritium

Topics: Ascomycota; Chemical Phenomena; Chemistry; Chromatography, Thin Layer; Cyclization; Ergolines; Ergot Alkaloids; Isomerism; Molecular Conformation; Photometry; Photosynthesis

Topics: Ascomycota; Cardiovascular Agents; Chemistry, Pharmaceutical; Claviceps; Ergolines; Ergot Alkaloids; Metabolism; Oxytocics; Research