Ergopeptines

Numerous ergopeptines have been isolated that have the same general structure but with substitutions at the amino acid positions in the tripeptide... 

Figure 1 Key intermediate and enzymes from the first committed step in ergot alkaloid biosynthesis through the synthesis of lysergic acid. Simple amides of lysergic acid and ergopeptines are covered in Figs 2 and 3, respectively. Abbreviations DMAPP = dimethylallyl pyrophosphate DMAT = dimethylallyl tryptophan AdoMet = S-adenosyl-methionine.

Figure 3 Biosynthesis of ergopeptines from lysergic acid. Ergovaline is presented as an example. Various other ergopeptines differ at amino acid positions I and II as indicated in the table, or, in one case, in position III as indicated in the text. The asterisk in the diagram of lysergyl-alanyl-valyl-proline lactam indicates the position of the carbon that is hydroxylated prior to cyclol ring formation.

Another possible advantage is conferred by deterrence of insect predation on the fungus or the plant that represents its food source. Ergopeptines in an artificial diet have been shown to deter feeding of adult beetles (Heteronychus arator)... 

Some nonribosomally synthesized peptides recognize and incorporate carboxy acids other than amino acids into nonribosomally synthesized peptides (Marahiel et al., 1997 von Dohren et al., 1997). Examples of non-amino acid substrates include 2-hydroxyvaleric acid in AM-toxin and enniatin, 2,3-dihydroxybenzoic acid in enterobactin, and lysergic acid in the ergopeptines. The incorporation of non-amino acids into peptides appears to be catalyzed by typical peptide synthetase modules (Haese et al., 1993 Gehring et al., 1998 Johnson et al., 2000). 

Annis SL, Panaccione DG. Presence of peptide synthetase genes transcripts and accumulation of ergopeptines in Claviceps purpurea and Neotyphodium coenophialum. Can J Microbiol 44 80-86, 1998. 

Ball OJP, Miles CO, Prestidge RA. Ergopeptine alkaloids and Neotyphodium lolii-mediated resistance in perennial ryegrass against adult Heteronychus arator (Coleoptera, Scarabaeidae). J Econ Entomol 90 1382-1391, 1997. 

Panaccione DG. Multiple families of peptide synthetase genes from ergopeptine-producing fungi. Mycol Res 100 429-436, 1996. 

Figure 3 Ergot alkaloid pathway in C. purpurea. (A) Ergoline ring biosynthesis up to lysergic acid. (B) Ergopeptine biosynthesis (ergotamin) starting from lysergic acid. (Modified from Tudzynski et al., 1998.)...

Hill NS, Thompson FN, Dawe DL, Stuedemann JA. Antibody binding of circulating ergopeptine alkaloids in cattle grazing tall fescue. Am J Vet Res 55 419-424, 1994. 

Hill NS, Parrott WA, Pope DD. Ergopeptine alkaloid production by endophytes in a common tall fescue genotype. Crop Sci 31 1545-1547, 1991. 

Rowan DD, Shaw GJ. Detection of ergopeptine alkaloids in endophyte-infected perennial ryegrass by tandem mass spectrometry. NZ Vet J 35 197-198, 1987. 

The change of Phe-340 to Leu-340 results in a severe loss in affinity for the mutant receptor of 5-HT, DOI and the eight ergolines tested with no effect on the affinity of ketanserin, ritanserin and the four ergopeptines tested except for ergocomine where the loss is moderate (about 5 fold). 

The affinities for the Leu-339 mutant receptor of the two ergopeptines tested ergotamine and ergocryptine did not differ from those for the wild type receptor. 

The ergopeptines probably owing to the size and conformation of the tricyclic substituent in the 8-position may bind to a (partly) different site on the receptor. The Phe-339 residue is important for the binding of ketanserin. 

Most typical ergot alkaloids have a lysergyltripeptide structure. One of the first known alkaloids of the ergopeptine type, eigotamine (Fig. 15), which was isolated and investigated by Stoll and Hofinann (207-209), on hydrolysis yielded (+)-lysergic acid, D-proline, L-phenylalanine, pyruvic acid, and 1 equiv of ammonia. The first two components occur in almost all... 

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