Ergot Alkaloids

Ergot alkaloids, produced by the ergot fungus Claviceps purpurea, have poisoned human populations that consumed bread baked from contaminated rye flour and caused an incalculable number of deaths (Chapter 9). Used in a deliberate fashion as medicines, the same compounds have alleviated the suffering caused by migraine headaches, treated symptoms of Parkinson’s disease, and stimulated uterine contractions and stemmed bleeding during childbirth. The toxicity and the therapeutic value of these compounds are due to their affinity for neurotransmitter receptors. The vasoconstriction leading to burning sensations associated with classic ergot poisoning, called St. Anthony’s fire in the Middle Ages, is caused by the neuronal stimulation of smooth muscle contraction. The effectiveness of the ergot alkaloids in treating migraine and reducing bleeding lies in the same pharmacological mechanism. Other species of Claviceps produce ergot alkaloids and the same pathway for toxin synthesis is found in different members of the family Clavicipitaceae, including endophytes in the genus Epichloë (= Neotyphodium) that cause toxicosis in animals browsing on contaminated grasses (Chapter 9). The human pathogen, Aspergillus fumigatus, and related saprotrophs are also sources of these compounds. The relationship, if any, between the synthesis of the alkaloids and the development of various forms of aspergillosis is not known.

Ergot alkaloids are a diverse category of secondary metabolites that have been classified into three groups as clavines, amides of lysergic acid, and ergopeptines. Lysergic acid diethylamide or LSD is a synthetic derivative of lysergic acid, which is a key intermediate in the biosynthesis of ergot alkaloids. Synthesis of most of the ergot alkaloids involves a common set of initial reactions beginning with the addition of a pyrophosphate group to tryptophan followed by a series of steps to produce a tetracyclic ergoline ring. Genes encoding the enzymes for these pathways are organized in clusters. Ergotamine and ergometrine, produced by Claviceps purpurea, are the most important of the alkaloids used in medicine and a number of derivatives of these compounds have been adopted for treating specific conditions. Commercial fermentation is the main source of ergot alkaloids today.