Ergot alkaloids.pptx

Ergot alkaloids

1. ERGOT ALKALOIDS P:3 U:2 Vedanti S. Gharat Roll No. :- 09 M.Sc. Biotech part 1

2. INTRODUCTION Alkaloids are a diverse group of small nitrogen containing organic compounds produced by certain plants and microorganisms. Species of the filamentous fungus Claviceps , which are pathogens of grasses, produce a range of alkaloids. Some of the best known are the ergot alkaloids . Ergot alkaloids  are a large group of compounds produced by species of the ascomycete fungus Claviceps that attack a wide variety of grass species, including small grains, during the growing season. They are also considered mycotoxins due to the severe toxic effects of ergot-contaminated grains on human and animal health, but some have various therapeutic properties. These compounds are produced within the sclerotia (fruiting bodies ) of Claviceps purpurea that develop naturally when this organism infects developing cereal grains. Infected grains become black and are referred to as ergots . These structures contain indole alkaloids, derived from a tetracyclic ergoline ring system.

3. These compounds are chemically divided into the C lavin  alkaloids, Lysergic acids, Simple lysergic acid amides and Peptide  alkaloids. Members of the first group are based on clavin and contain no peptide component. Clavin-based alkaloids are also produced by other groups of fungi, including species of Aspergillus and Penicillium . Some possess antibiotic and antitumor activity, but few are produced commercially. The second group, based on lysergic acid (LSA) and containing a tripeptide or an amino alcohol, are found only in Claviceps species. Examples include ergometrine, ergocristine, ergosine and ergotamine.

4. Ergotamine , Dihydroergotamine and ergometrine, produced by Claviceps purpurea , are the most important of the alkaloids used in medicine. These LSA-based alkaloids have medical roles as analgesics in migraine therapy, as hallucinogens and for treating circulation problems. Ergotamine , for example, is a structural analogue of serotonin (a neurotransmitter) and is formed from LSA by the action of a peptide synthetase that adds alanine, proline and phenylalanine . Others have particular uses in obstetrics, for inducing the smooth muscle of the uterus to contract during labour and after childbirth.

5. PRODUCTION OF ERGOT ALKALOIDS There are no. of methods of obtaining ergots alkaloids: Chemical synthesis Culture of Claviceps strain on the respective host. Microbial fermentation Surface culture with immobilized cells Commercial fermentation is the main source of ergot alkaloids today . Previously , the alkaloids were extracted from ergots that developed within infected cereal crops, usually rye, or by chemical synthesis. Most are now produced by fermentation of Claviceps fusiformis , C . paspali or C . purpurea in surface, submerged or immobilized cell culture. The structure of  EA  was determined by High Performance Liquid Chromatography ( HPLC ) /positive ion Atmospheric Pressure Chemical Ionization Mass Spectrometer ( APCI MS ) and Nuclear magnetic resonance spectroscopy  ( NMR analysis ).

6. CHEMICAL SYNTHESIS Total chemical synthesis of ergots alkaloid is possible, but currently this not cost effective. Lysergic acid which is produced fermentatively can be chemically transformed into the desired alkaloids. Ergoline derivatives used medically using this method, with the exception of peptide bonds. SURFACE CULTURE A process has been described for the large scale production of ergot alkaloids using surface cultures of C . purpurea grown under sterile conditions. The advantage of this process is that a higher proportion of the more desirable ergotamine and ergotoxine alkaloids are formed.

7. SEMI CONTINUOUS TRANSFORMATION WITH IMMOBILIZED MYCELIUM A process has been developed for Semi continuous transformation using immobilized mycelium of C . purpurea and C. fusiformis . C . purpurea which forms Ergometrine and mixture of chanoclavin, agroclavin and elymoclavin, the best result has been obtained by immobilization in 4% calcium alginate gel . Concentration of algine increases to 8% - yield of alkaloid increased by 35%, but the main product is agroclavin due to reduced oxygen diffusion . To prevent contamination problem during the long incubation period with the immobilized mycelium, an antibiotic chloramphenicol was added.

8. PRODUCTION BY FERMENTATION Three species of Claviceps are currently used in the production of alkaloids by fermentation. C. fusiformis C . paspali C . purpurea Submerged culture produced about 20mg of alkaloid/L. Strain development and culture medium optimization resulted in a commercial process which had alkaloid titres of 5g/L. Stages of fermentation process

9. Inoculum for the production fermenter may be developed from mycelium or conidiospores. The production medium contains an organic acid of the tricarboxylic acid (TCA) cycle and a carbohydrate, such as citrate and sucrose, the specific combination depending upon the target alkaloid. In later stages, the organic acid stimulates the necessary metabolic change from the TCA cycle to the glyoxylate cycle. Alkaloid production, like that of many secondary metabolites, exhibits phosphate regulation . Primary metabolism pathway occurs at the growth phase and is also known as  trophophase  while the secondary metabolism pathway occurs at the stationary phase and is also known as  idiophase . The synthesis is delayed until the medium phosphate has been utilized during the trophophase and the culture enters the idiophase. However, phosphate inhibition can be overcome by addition of tryptophan or a tryptophan analogue, which act as inducers and precursors.

10. PHARMACOLOGICAL PROPERTIES Stimulation of sympathetic nervous system. Ergovanine is used to hasten labor and prevent postpartum bleeding. Ergotamine is a compound produced by Claviceps purpurea and is a powerful vasoconstrictor, which means it constricts the blood vessels and thus the blood flow. A mixture of dihydro-compounds from ergocristine, ergocriptine and ergocornine is used for treatment of disturbances of peripheral and central circulation system.

11. REFERENCES Notes Industrial microbiology by Morgan and Higton. Images from Google. thank you