FIG 1.

Pathways to the synthesis of lysergic acid amides and dihydrolysergic acid amides. Both pathways begin with the same core set of genes (dmaW, easF, easE, easC, and easD) and branch at easA depending on the allele present in a species. The pathway branch to the right (with red labeling) leads to lysergic acid amides, as are found in M. brunneum (26), with a further branch to ergopeptines (labeled in orange), as found in Claviceps purpurea and several Epichloë species (1, 2, 9). Red font is used to mark the carbons present in the D ring of ergoline nucleus. The pathway branch to the left (with blue labeling) leads to dihydroergot alkaloids as found naturally in C. africana (45) or in previously engineered strains of N. fumigata (18, 19). The dihydroergot alkaloid pathway features a further branch, shown in pink, that occurs in no natural species but whose formation is a subject of this paper. Double arrows represent multiple enzymatic steps. Enzymes with hypothesized roles are marked by parentheses. Trp, l-tryptophan; DMAPP, dimethylallylpyrophosphate.