Ergot alkaloids, biosynthesis

Ergot Alkaloids.—4-(yy-Dimethylallyl)tryptophan (122) is the first intermediate beyond tryptophan in ergot alkaloid biosynthesis. Chanoclavine-I (127) is the first tricyclic base (cf. Vol. 10, p. 26, and ref. 2). Recently, (124 labels as shown) has been found to be a very efficient and intact precursor for elymoclavine (128).45 The high level of incorporation indicates that (123) is a probable intermediate situated between (122) and (127). The decarboxylation product (125) was not utilized for biosynthesis, so, although decarboxylation of (123) is required for the conversion of (123) into (127), either it is intimately associated with ring-closure or an imine that is related to (126) is involved. 

Ergot Alkaloids.—The enzyme which catalyses the first step in ergot alkaloid biosynthesis, namely the conversion of tryptophan into dimethylallyltryptophan (126),110 has been isolated from a Claviceps species and characterized.111 The biosynthesis of clavicipitic acid (127) may be a major alternative to the synthesis of other ergot metabolites, and further results in a study112 of an enzyme from C. purpurea which catalyses the formation of clavicipitic acid (127) from (126) have been published.113... 

Experiments have been carried out with elymoclavine (73) in whole cells and protoplasts of Claviceps strain SD 58 levels of dimethylallyltryptophan synthetase, the first enzyme in ergot alkaloid biosynthesis, were measured.64 The results that were obtained provide strong evidence that there is end-product regulation of the synthesis of alkaloids in vivo and that it involves feedback inhibition end-product repression of the synthesis of enzymes appears to be of lesser importance. 

Shibuya, M., Chou, H.-M., Fountoulakis, M., Hassam, S., Kim, S.-U., Kobayashi, K., Otsuka, H., Rogalska, E., Cassady, J.M. and Floss, H.G. (1990) Stereochemistry of the isoprenylation of tryptophan catalysed by 4-( Y, Y-dimethylallyl)tryptophan synthase from Claviceps, the first pathway-specific enzyme in ergot alkaloid biosynthesis. /. Am. Chem. Soc., 112, 297-304. 

Molecular Genetics of Ergot Alkaloid Biosynthesis Daniel G. Panaccione and Christopher L. Schardl... 

Molecular Aspects of Host-Pathogen Interactions and Ergot Alkaloid Biosynthesis in Claviceps Paul Tudzynski and Klaus B. Tenberge... 

Wang J. dmaW encoding tryptophan dimethylallyltransferase in ergot alkaloid biosynthesis from Clavicipitaceous fungi. PhD dissertation, University of Kentucky, Lexington, KY, 2000. 

Tsai H-F, Wang H, Gebler JC, Poulter CD, Schardl CL. The Claviceps purpurea gene encoding dimethylallyltryptophan synthase, the committed step for ergot alkaloid biosynthesis. Biochem Biophys Res Commun 216 119-125, 1995. 

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.

GENES ENCODING ENZYMES INVOLVED IN ERGOT ALKALOID BIOSYNTHESIS... 

Kozikowski AP, Wu J-P, Shibuya M, Floss HG. Probing ergot alkaloid biosynthesis identification of advanced intermediates along the biosynthetic pathway. J Am Chem Soc 110 1970-1971, 1988. 

GENETICS OF ERGOT ALKALOID BIOSYNTHESIS 4.1. Biochemistry and Pharmacology... 

Dimethylallyltryptophan (139) has been identified as the first intermediate after tryptophan in ergot alkaloid biosynthesis.In experiments with a Claviceps species, clavicipitic acid (140) was identified as a major product formed from (139).(The enzyme catalysing this transformation was identified in both the supernatant and microsonal fractions oxygen is necessary for the reaction but cytochrome P-450 does not appear to be involved.) But radioactive clavicipitic acid was found to be a much less efficient precursor than (139) for elymoclavine and thus is in all probability not an intermediate in ergot alkaloid biosynthesis. 

There has been a steady progress in the fitting together of the pieces that make up the pattern of furoquinoline and ergot alkaloid biosynthesis so that the pathways for each of these groups is now fairly clear. Both have been the subject of recent publication (see p. 35 and 27). 

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