Ergot (Claviceps purpurea), best known as a disease of rye and some other grasses, is probably the most widely cultivated fungus and has now become an important field crop. The main reason for its importance is the presence of ergot alkaloids, extensively used in medicine. Currently, ergot alkaloids cover a large field of therapeutic uses as drugs of high potency in the treatment of uterine atonia, postpartum bleeding, migraine, orthostatic circulatory disturbances, senile cerebral insufficiency, hypertension, hyperprolactinemia, acromegaly, and parkinsonism. Recently, new therapeutic uses have emerged, such as, e.g., against schizophrenia, applications based on newly discovered antibacterial and cytostatic effects, immunomodulatory and hypolipemic activity.
Of the naturally occurring ergot alkaloids only two are used in the therapy: ergotamine and ergometrine. The rest of the therapeutically important ergot compounds are semisynthetic compounds.
Ergot alkaloids are traditionally obtained by extraction of ergot sclerotia artificially cultivated on cereals. The parasitic cultures are not able to produce all alkaloids, e.g., clavine, necessary for most semisynthetic drugs. Crop fluctuations and market demand have led to the development of saprophytic cultivation in production plants. Submersed cultures of various Claviceps strains produce relatively high yields of clavines or lysergic acid derivatives, e.g., elymoclavine and paspalic acid.
Present trends in ergot cultivation are the development of saprophytic cultivation processes and the improvement of field production such as the introduction of new hosts and ergot strains. In spite of constant effort to prepare ergot alkaloids synthetically, their bioproduction is still economically more competitive.
Ergot in Agriculture
Ergot – once dreaded as a pest and the cause of epidemic intoxications has now become a very profitable crop for farmers; however, the danger of intoxication and crop damage still persists.
Field Production of Ergot Alkaloids
Ergot is a good and profitable alternative crop for farmers. The price for ergot as a raw material for the pharmaceutical industry is established by the situation on the market. The price of ergot grown parasitically is approximately 80% higher than the price of the cereals produced on the same area. However, special investments are necessary for ergot cultivation (inoculation machines, special seed material). Total expenses depend on the area and the time of ergot production. Nevertheless, these investments lower the profit by about 10%. The profits from ergot cultivation are stilll higher in the countries with lower labor costs, e.g., Central and Eastern Europe (up to 180%).
Ergot in Europe is produced parasitically in Switzerland, Germany, Spain, Austria, Poland, the former Yugoslavia, Czech Republic, and Hungary. Production varies from year to year depending on the market situation.
Ergot has been artificially cultivated since 1942, when A. Stoll at Sandoz Ltd. (Basel) developed an inoculation machine based on pricking the ears with infected needles. Since that time, many variations of this machine have been constructed, the principle, however, remaining the same. The main part of the machine consists usually of pairs of vertically arranged cylinders rotating in opposite directions. One cylinder of each pair is equipped with needles and the other has a smooth (rubber) surface that gently presses the ears against the needles. The spore suspension is directed from a storage tank through pipes over the needles. The inoculation of the plants is repeated after several days. The dose of conidia is usually 1012/ha.
Inoculation material (spores) is prepared either by surface or by submerged saprophytic cultivation. The first method (surface) is rather laborious but the spores are of good quality and can be stored, after drying, for a long time without loss of viability. The substrate is usually represented by sterilized rye grains soaked in a nutritive medium. The cultivation proceeds in bottles. Alternatively, cultivation in plastic bags on the surface of the liquid medium can be performed. The mycelia with the spores are then collected, dried, and powdered.
Submerged preparation of the inoculum is analogous to the submerged production of ergot alkaloids. However, in the submerged culture, nonuniform conidia or blastospores develop, having good infectivity but lower viability (after drying). This problem was solved by the addition of 1-2% suspension of Siloxide (fine hydrophic silica gel) to the fermentation broth containing spores and mycelium. The resultant mixed suspension is then filtered, gently dried, and granulated. The resulting product is of good viability and storability, and is easy to handle.
The strains used for preparation are carefully bred with respect to total ergot alkaloid content in sclerotia, to the type of alkaloids produced, and to infectivity. Typically, industrial strains produce, e.g., α-ergokryptine, ergocristine, or ergotamine. Some strains produce directly a mixture of alkaloids necessary for a particular medicine preparation so that the separation step can be reduced (e.g., ergocornine-ergokryptine strains). Yields of the field cultivation are 700 to 1200 kg/ha; the total alkaloid content ranges from 0.4 to 1.2%.
An important factor in ergot yields is the host cereals. Rye is the most typical host for ergot in nature and also in artificial parasitic production. Triticale and wheat are used for ergot production and show good yields. An introduction of male sterile lines of some cereals, namely of rye, was a qualitative step forward in the field production of ergot. The florets remain open until the ovaries are effectively pollinated. The chances of ergot spores gaining entry to the florets and causing infection of the ovaries are thereby greatly increased. This is especially the case in secondary infection (after artificial inoculation) caused by honeydew that can reach the rest of the ovaries not punctured by inoculating needles. Finally, up to 100% of all ovaries in the ear are infected which increases the ergot yield dramatically. Another advantage is that the sclerotia are nearly uniform and do not fall out from the ears before harvest. The harvest is done by normal combined harvesters without any modifications, thus no hand picking or “brushing” is necessary.
Male sterile rye (genetically or cytoplasmatically inherited) is selected by the known methods and marketed for the above purposes. In Europe a brand Hyclaro is produced by Rentschler Co., (Laupheim, Germany).
Biotechnology of Claviceps purpurea (ergot) producing ergot alkaloids is discussed. Both parasitic (field production) and saprophytic cultivation of the ergot strains are described. C. purpurea in agriculture was considered to be dangerous pest, but has recently become an important crop. Bioproduction of ergot alkaloids by submerged fermentation employing various modern techniques such as immobilization, plant cell cultures, and biotransformation, is described.
Ergot alkaloids have a long history and, without doubt, also a promising future. The demand for this commodity is constantly growing, so that more effective technologies must be developed.