Biosynthetic studies on some polyene mycotoxins

Citreoviridin, asteltoxin and aurovertin B are members of a group of mycotoxins which act as inhibitors of oxidative phosphorylation in rnitochondria. The biosynthetic origin of the carbon skeleton of these metabolites was studied by incorporation of 13C—labelled precursors: [l—'3C]—, [2—'3C]—, [l,2—'3C2]—, [l—'3C,2—2H3—, and 12—'3C,2—2H3]acetate, (25)—[methyl— 13C ]methionine and [1— 3C]— and [3—13C]propionate. The results show that aurovertin B and asteltoxin can be formed via two biosynthetic pathways. The first pathway involves the methylation of an eventual C20—polyketide, followed by loss of the chain—initiating acetate unit. The second pathway involves a poly— ketide precursor formed from a propionate chain—initiating unit and eight malonate units. In addition the arrangement of intact acetate 13 units in asteltoxin derived from [1,2— C2]acetate proves that a 1,2—bond migration occurs during the formation of the 2,8—dioxabicyclo— [3.3.0]octane moiety. Citreoviridin is derived from a C18—polyketide formed from an acetate chain—initiating unit and eight malonate units. r 13 18 1 18 . . . Incorporation of L1— C, O2jacetate and 02 gas into citreoviridin, aurovertin B, and asteltoxin established the origin of the oxygen atoms and provided stereochemical and mechanistic information on the biosynthetic pathways of these metabolites. The incorporation of (25)— [methyli3C]methionine and [1,2—13C2]acetate into the fusarins, metabolites of Fusarium moniliforme, points to a biosynthetic pathway involving the condensation of a C1z—polyketide and a Cif intermediate, e.g. oxaloacetate, of the Krebs tricarboxylic acid cycle.