Biosynthesis of aspergiolide A, a novel antitumor compound by a marine-derived fungus Aspergillus glaucus via the polyketide pathway

Aspergiolide A, a novel antitumor compound, was produced by a marine-derived filamentous fungus Aspergillus glaucus. The biosynthesis of it was unambiguously determined by feeding experiments using [l-13C]sodium acetate, [2-13C]sodium acetate, and [1,2-13C2]sodium acetate precursors followed by 13C NMR spectroscopic investigation of the isolated products. Analysis of the patterns of 13C-enrichment revealed that all 25 carbon atoms in skeleton of aspergiolide A were derived from labeled acetate. And among them, 12 carbon atoms were labeled from the carboxylic group of acetate, while the other 13 carbon atoms were labeled from the methylic group of acetate. Besides, the labeling pattern of [1,2-13C2]sodium acetate feeding experiment demonstrated that 12 intact acetate units were incorporated in aspergiolide A by polyketide pathway.