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Review
, 7 (1), 201-18

Diversification of Ergot Alkaloids in Natural and Modified Fungi

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Review

Diversification of Ergot Alkaloids in Natural and Modified Fungi

Sarah L Robinson et al. Toxins (Basel).

Abstract

Several fungi in two different families--the Clavicipitaceae and the Trichocomaceae--produce different profiles of ergot alkaloids, many of which are important in agriculture and medicine. All ergot alkaloid producers share early steps before their pathways diverge to produce different end products. EasA, an oxidoreductase of the old yellow enzyme class, has alternate activities in different fungi resulting in branching of the pathway. Enzymes beyond the branch point differ among lineages. In the Clavicipitaceae, diversity is generated by the presence or absence and activities of lysergyl peptide synthetases, which interact to make lysergic acid amides and ergopeptines. The range of ergopeptines in a fungus may be controlled by the presence of multiple peptide synthetases as well as by the specificity of individual peptide synthetase domains. In the Trichocomaceae, diversity is generated by the presence or absence of the prenyl transferase encoded by easL (also called fgaPT1). Moreover, relaxed specificity of EasL appears to contribute to ergot alkaloid diversification. The profile of ergot alkaloids observed within a fungus also is affected by a delayed flux of intermediates through the pathway, which results in an accumulation of intermediates or early pathway byproducts to concentrations comparable to that of the pathway end product.

Figures

Figure 1
Figure 1
Early steps of the ergot alkaloid pathway. AdoMet, S-adenosylmethionine; DMAPP, dimethylallylpyrophosphate.
Figure 2
Figure 2
(a) Significant branch points in the ergot alkaloid pathway of several fungi. Steps and intermediates common to all ergot alkaloid producers are labeled with black text. The major branch to lysergic acid derived-ergot alkaloids followed by most fungi in the Clavicipitaceae is labeled in green. The branch leading to festuclavine is labeled with purple, and then branches after festuclavine are labeled in blue (for the dihydroergot alkaloids of C. africana and C. gigantea) or red (for the fumigaclavines of the Trichocomaceae). The same color scheme is used in all figures; (b) Position numbering and ring labeling used in text and figures.
Figure 3
Figure 3
Diversification in the major branch of the ergot alkaloid pathway occurring in the Clavicipitaceae. Steps represented by arrows without enzyme labels occur spontaneously. Dashed arrows indicate hypothesized steps that have not been experimentally demonstrated. R groups in the ergopeptine structure represent side chains for amino acids listed in Table 1.
Figure 4
Figure 4
Pathway of dihydroergot alkaloids in C. africana or C. gigantea. The pathway in C. gigantea ends at dihydrolysergol, whereas that of C. africana extends to dihydroergosine. Roles for all enzymes are hypothesized based on analogy with Epichloë species and C. purpurea.
Figure 5
Figure 5
(a) Diversification of ergot alkaloids in the Trichocomaceae. Some isolates of N. fumigata terminate their pathway at fumigaclavine A, whereas others produce fumigaclavine C [56]. Penicillium commune lacks easL [27] and terminates its pathway at fumigaclavine A. The role of prenyl transferase EasL (also called FgaPT1) in producing fumigaclavine C (and presumably 9-deacetoxyfumigclavine C and 9-deactylfumigaclavine C) is indicated; (b) Pathway resulting from expression of easAisomerase in N. fumigata easA ko. The role of EasL in prenylating agroclavine [26] is indicated. Peroxidases common to N. fumigata and many organisms [40,60] oxidize agroclavine to setoclavine. Alternate routes for production of prenylated setoclavine [26] are indicated. (c) 8S,9S fumigaclavine A compared to 8R,9S fumigaclavine A. Alkaloids typically found in the Clavicipitaceae are labeled with green. Dashed arrows indicate hypothesized steps.

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