Introduction to Fungi, Third Edition

354 HYMENOASCOMYCETES: PYRENOMYCETES
Fig12.28 Biosynthesis of alkaloids in ergots of Claviceps purpurea. Starting from tryptophan and the mevalonic acid-derived metabolite
dimethylallylpyrophosphate, dimethylallyltryptophan is synthesized. Ring closure, decarboxylation and addition of a methyl
group from methionine (arrowhead) gives the simplest alkaloids, agroclavine and D-lysergic acid.The latter is then derivatized at its
C-8 position to give more complex alkaloids such as ergometrine and ergotamine. LSD (D-lysergic acid diethylamide) is a semisynthetic
derivative of D-lysergic acid.
and a haemostatic drug. It was also the first
medication available against migraine (Eadie,
2004). A third ergot-derived drug is lysergic acid
diethylamide (LSD), a synthetic derivative of
lysergic acid. As is well known, this drug has
hallucinogenic properties and is associated with
euphoria (Minghetti & Crespi-Perellino, 1999).
Numerous chemical derivatives have been
synthesized, and ergot alkaloids are lead structures
for drugs against a range of illnesses,
including Parkinson’s disease and Alzheimer’s
disease.
The biosynthesis of ergot alkaloids in
C. purpurea from tryptophan, mevalonic acid
and methyl groups donated by methionine
leads to the ergoline ring structure (Fig. 12.28).
The simplest alkaloids are the clavine alkaloids
such as agroclavine, but most of the pharmaceutically
important ones are based on D-lysergic
acid because it is the carboxylic acid group at C-8
in D-lysergic acid which is further substituted.
Simple substituted D-lysergic acid derivatives
are ergometrine and the semi-synthetic LSD
(Fig. 12.28). In the most complex ergot alkaloids,
the ergopeptines, three amino acids are added
to D-lysergic acid by a non-ribosomal peptide
synthase, followed by ring closure. Ergotamine
is a commonly found example of this type of
alkaloid in C. purpurea (Fig. 12.28). Reviews of
alkaloid biosynthesis have been written by
Flieger et al. (1997) and Tudzynski et al. (2001).
A concise general treatment is that by Lohmeyer
and Tudzynski (1997).
The ergot of commerce is produced by cultivating
the fungus on rye, and profitable crops
of ergot sclerotia are obtained, often on specially
bred strains of male-sterile rye in Eastern Europe,
Spain and Portugal (Németh, 1999). Rye flowers
are infected with a suspension of conidia from
strains of C. purpurea selected for high yield of
certain alkaloids. Alkaloids are extracted from
harvested sclerotia. Alkaloids are also extracted
from special strains of C. purpurea grown saprotrophically
in deep fermentation. About 60% of