Studies on the Biosynthesis of Ergot Alkaloids

Abstract

DL-'l'ryptophan-P-C", but not L-phenylalanine-U-CL' nor ~-t v r o s i~l e -U -C~-~, is incorporated into the ergoline moiety of the ergot allialoids. The high specific activities of the bases isolated from cultt~res supplemented with a mixture of ~L -t r y~t o~h a n -P -C l~a n d carrier L-tryptophan indicate some contribution from the D-isomer.

Biosynthesis of ergotamine by Claviceps purpurea (Fr.) Tul

“…These results were expected in the light of other work (Groger et al, 1960;Taylor & Ramstad, 1960;Birch et al, 1960;Vining & Taber, 1963;Agurell, 1966;Majer et al, 1967;Castagnoli et al, 1970) the lysergic acid moiety of ergotamine is similar to that found for the other ergot alkaloids.…”

“…Both L-[U-14C]phenylalanine and L-[U-14C]proline were found to be specific precursors for the constituent side-chain phenylalanine and proline moieties of ergotamine, confirming and extending the findings of Vining & Taber (1963) and Groger & Erge (1970). The fact that proline was not quite so specific a precursor as phenylalanine probably reflected the ease with which proline enters the tricarboxylic acid cycle through ready conversion into glutamate and ax-oxoglutarate; thus some random distribution of label supplied as proline may be expected.…”

“…However, it has been demonstrated that the same ergoline precursors, namely tryptophan and indole (Paul, 1957;Baxter et al, 1960Baxter et al, , 1961Taber & Vining, 1959;Vining & Taber, 1963;Groger & Erge, 1970), mevalonic acid (Baxter (I) Ergotamine et al, 1961;Taylor & Ramstad, 1960) and the methyl group of L-methionine (Majer et al, 1967;Castagnoli et al, 1970), function as specific precursors for the lysergic acid moiety of the peptide alkaloids.…”

“…Of the studies that have been carried out, Paul (1957), using a sclerotial homogenate, and Vining & Taber (1963), using a low-yielding surface culture of Clavicepspurpurea, both demonstrated that alanine and phenylalanine were incorporated into the alkaloid, but the specificity of incorporation was not established. Majer et al (1967) found that radioactivity from L-[U-14C]alanine was incorporated into the whole ergotamine molecule and only 12 % of the label was associated with the oc-hydroxy-a-alanine moiety.…”

Microdegradation Procedure for Radioactive Peptide Ergot Alkaloids

“…Moreover, cardiovascular studies in the anesthetized intact dog and cat have demonstrated a significant blockade of the pressor response to exogenous epinephrine, with doses of cryogenine having no apparent effect on resting blood pressure (2,5).…”