Ergot alkaloids agroclavine biosynthesis

A fascinating problem in the biosynthesis of ergot alkaloids is the mechanism by which dimethylallyltryptophan (102) is transformed through chanoclavine-I (103) to agroclavine (104) and elymoclavine (106), a reaction sequence which involves two cis-trans isomerizations in the side-chain double bond. Further evidence on the course of biosynthesis comes from feeding dimethylallyltryptophan labelled as shown in (102), to Claviceps penniseti. The alkaloids (103), (104), and (106) were isolated and the sites of labelling were determined to be as shown in Scheme 7. Thus the first double bond isomerization occurs between (102) and (103) and the second between (103) and (104). 

The biosynthesis of ergot alkaloids is initiated by prenyla-tion of tryptophan with dimethylallyl pyrophosphate (DMAPP) to yield 4-dimethylallyltryptophane (DMAT) (4) (Fig. 35.2) (Floss, 1980). This alkylation step is believed to be rate limiting, and the enzyme that catalyzes this reaction, DMAT synthetase, has been purified more than 60 times (Maier and Groger, 1976 Waller and Dermer, 1981). The enzyme appears to be specific for L-tryptophan and is inhibited by agroclavine (2) and elymoclavine (5) the end products of the reaction. 

Matuschek M, Wallwey C, Xie X, Li S-M (2011) New insights into ergot alkaloid biosynthesis in Claviceps purpurea an agroclavine synthase EasG catalyses, via a non-enzymatic... 

Shough HR, Taylor EH (1969) Enzymology of ergot alkaloid biosynthesis. Part IV. Additional studies on the oxidation of agroclavine by horseradish peroxidase. Uoydia/J Nat Prod 32 315-326... 

Agurell, S. (1966b) Biosynthesis of ergot alkaloids in Claviceps paspali. II. Incorporation of labelled agroclavine, elymoclavine, lysergic acid and lysergic acid methyl ester. Acta Pharm. Suec., 3, 33-36. 

Voigt and Zier (1970, 1971) proposed that the biosynthesis of ergot alkaloids could occur by the pathway dihydrochanoclavine I dihydro-agroclavine -> agroclavine elymoclavine. In experiments with ripening... 

Four enzymes which are involved in the biosynthesis of the ergot alkaloids have now been isolated from Claviceps. The other three are 4-dimethylallyltryptophan synthase , chanoclavine-I cyclase , and agroclavine hydroxylase . ... 

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