2. ALKALOIDS
Alkaloids are a group of naturally occuring chemical
compounds that mostly contain basic nitrogen atoms.
Alkaloids are produced by a large variety of organisms
including bacteria, fungi, plants, and animals.
They can be purified from crude extracts of these organisms
by acid-base extraction
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4. Ergot alkaloids
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.
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5. Occurrence:
Ergot alkaloids were first developed from the
sclerotium of the parasitic ascomycete Claviceps
purpurae, which developes on rye and other
grasses.
The term ERGOT is used to refer both to the
fungus developing in the rye plant and to the
alkaloids which are produced by the fungus.
Presently there are 40 known ergot alkaloids
produced by various Claviceps strains.
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6. Pharmacological properties:
Stimulation of the 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 dihydrocompounds from
ergocristine , ergocriptine , and ergocornine is
used for treatment of disturbances of preipheral
and central circulation system
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11. structure
Ergot alkaloids are classified among the indole alkaloids
and are derived from the tetracyclic ergoline ring system.
Ergot alkaloids are classified into two classes
1) Clavine alkaloids or Clavines : Have ergoline as
a basic structure but contain no peptide bonds.
EX: Festuclavine , Dihydroelymoclavine ,
etc.,
2) Lysergic acid alkaloids or Ergo alkaloids :In
these component D-lysergic acid is linked with tricyclic
peptide.
EX: Ergometrine , Ergocorine , etc.,
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13. biosynthesis
Alkaloids synthesis occurs upon the endoplasmic
reticulum in claviceps when it is grown in
submerged culture.
FORMATION OF ERGOMETRINE FROM
MEVALONATE
Mevalonate
Isopentenyl pyrophosphate
Dimethylallyl pyrophsphate
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20. Production of ergot alkaloids
There are a number of methods of obtaining ergot
alkaloids:
Chemical synthesis
Culture of Claviceps strains on the respective host
Microbial fermentation
Surface culture
With immobilized cells
Culture on the host plant or in submerged culture are
the process most used commercially.
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21. Chemical synthesis
Total chemical synthesis of ergot alkaloids is
possible, but currently this is 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.
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22. Surface culture:
A process has been described for the large-
scale production of ergot alkaloids using
surface cultures of C.purpurae grown
under sterile conditions.
The advantage of this process is that a
higher prportion of the more desirable
ergotamine and ergotoxine alkaloids are
formed.
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23. Semicontinuous transformation with immobilized
mycelium
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A process has been developed for semicontinuous
alkaloid production using immobilized
mycelium of Claviceps purpurae and
C.fusiformis.
C.purpurae which forms Ergometrine and and
mixture of chanoclavin , agroclavin and
elymoclavin , the best results has been obtained by
immobilization in 4% calcium alginate gel.
24. Contd.,
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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 contaminaton problem during the long
incubation period with the immobilized mycelium,
an antibiotic chloromphenicol was added.
25. Production by fermentation
Three species of Claviceps are currently used in the
production of alkaloids by fermentation.
C.paspali
C.fusiformis
C.purpurae
Submerged culture produced about 20mg alkaloid/l
Strain development and culture medium optimization
resulted in a commercial process which had alkaloid
titres of 5g/l
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26. Stages of fermentation process:
Homogenized mycelium of a 5-10day agar slant culture
conidium suspension
Growth in shake flask
Preculture
48 hour
Production culture
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27. Regulationn of alkaloid production in cultures:
To produce alkaloids the medium must contain an
organic acid of the TCAcycle or a related
compound as well as carbohydrate.
Mannitol and succinate : production of lysergic
acid.
Sucrose and citrate : production of Ergotamine and
Ergocristine.
Ergot alkaloid production exhibits a typical
phosphate regulation.
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28. Contd.,
In the trophophase (3-4 days), after free
phosphate used up, growth ceases and the culture
enters the idiophase.
Tryptophan induces alkaloid synthesis and serves
as a precursor.
In submerged culture, synthesis of the alkaloid is
increased considerably when aspargine is used as a
Nitrogen source instead of ammonium salts.
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