Studies on the biosynthesis of the mycotoxin austin, a meroterpenoid metabolite of Aspergillus ustus

Abstract

Incorporations of l3C-labeIled acetates and methionine into the mycotoxin austin in cultures of Aspergillus ustus give a labelling pattern consistent with a mixed polyketide-terpenoid pathway. Incorporations of 14C and *H labelled 3,5-dimethylorsellinate confirm the intermediacy of a preformed tetraketide-derived phenolic precursor. Further information on the mechanisms involved in the modifications of both the farnesyl-and tetraketide-derived portions of the molecule are provided by i n c o r po ra t i o n stud i es with [ 1 -3C, 0 ,I acetate, [methyl-C ,* H 3] met h ion i ne, 3C, 8O -I a be I I ed d i m et h y Iorsellinate, I8O2 gas and [6-13C,6-*H3] mevalonic acid lactone. Aspergillus 11stii.5, one of the most prevalent fungi in soil and decaying vegetation, is a known contaminant of stored foodstuffs such as cereals, pulses and cheese and is known to produce a number of toxic secondary metabolites of varied biosynthetic origin.The first secondary metabolite isolated from A . ustus in 1951

Two Separate Gene Clusters Encode the Biosynthetic Pathway for the Meroterpenoids Austinol and Dehydroaustinol in Aspergillus nidulans

“…Simpson’s group proposed that this rearrangement involves hydroxylation of the C-5', followed by α-ketol rearrangement and reduction of the ketone with lactone formation by the attack of the hydroxyl group on the carboxy group. 12 Our results show that these steps of the pathway involve at least four genes ausJ , ausK , ausH , ausI . The ausJ deletant accumulated compound 5 (Fig.…”

“…A similar compound was proposed earlier as a key early intermediate in austin biosynthesis. 12 Protoaustinoid A contains a methyl ester connected to carbon 8' instead of the carboxylic function group in the previously proposed structure. 12 …”

“…12 Since the genes involved in the biosynthesis of particular secondary metabolites are usually clustered in fungi, 22 we wished to delete genes surrounding ausA and ausN to identify other genes required for austinol and dehydroaustinol biosynthesis. A problem with respect to the ausA region was that there was a gap near ausA in the genome (i.e.…”

Structures of meroterpenes produced by Penicillium sp, an endophytic fungus found associated with Melia azedarach

“…22 These reactions can be used to tentatively explain the origin of the spiro system present in the meroterpenoids (Austin's derivatives). 23 The similarity found in these two classes of secondary metabolites may be due to the presence of the same or very similar enzymatic system in the fungus and the plant. This may have resulted from a lifetime of intimate biochemical association.…”

“…21 The α, β-unsaturated-δ-lactone present as part of a spiro system in the A/B rings of meroterpenoids 1, 2, 3 and 4 is similar to the partial structures of some limonoids (see 6, and 7). 22,23 The main reactions involved in limonoid biosynthesis are Baeyer-Villiger-type oxidation and structural rearrangements. 22 These reactions can be used to tentatively explain the origin of the spiro system present in the meroterpenoids (Austin's derivatives).…”