This document discusses ergot alkaloids, which are compounds produced by the fungus Claviceps that attacks various grass species. There are several types of ergot alkaloids, including clavine alkaloids, lysergic acid derivatives, and peptide alkaloids. Ergot alkaloids can be produced through chemical synthesis, fermentation, or by extracting them from infected cereal crops. Commercial fermentation using species like C. fusiformis, C. paspali or C. purpurea is now the main production method. The fermentation process involves growing the fungus in a nutrient medium to produce the alkaloids. Some important medically used ergot alkaloids include ergotamine, di

1. ERGOTALKALOIDS
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.

4. • These compounds are chemically divided into the
1. Clavin alkaloids,
2. Lysergic acids,
3. Simple lysergic acid amides and
4. 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.

5. • 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.

7. 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).

8. 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.

9. 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.

10. PRODUCTION BY FERMENTATION
• Three species of Claviceps are
currently used in the
production of alkaloids by
fermentation.
1. C. fusiformis
2. C. paspali
3. 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
Homogenized mycelium of
a 5-10 day agar slant culture
(conidium suspension)
Growth in shake flask
Preculture (48 hrs)
Production culture

11. • 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.

12. 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.

13. REFERENCES
• Notes
• Industrial microbiology by Morgan and Higton.
• Images from Google.