The biosynthesis of the potent carcinogens aflatoxin B1 and G1 is to be investigated. These mycotoxins occur widely in many parts of the world as food contaminants and are an important environmental health hazard. A broad-based program is outlined involving (1) the synthesis and testing of potential intermediates for incorporation into aflatoxin B1 in whole cells of Aspergillus parasiticus will be undertaken in 3H/14C-, 2H/13C- and 13C/180-labeled form as, for example, 5'-ketoaverythrin, 1'-hydroxyversicolorone, 6-deoxyversicolorin A and potential ortho-carboxybenzophenones and dienones of the bisfuran and xanthone formation and rearrangement steps; (2) the examination of apparent Baeyer-Villiger oxidations; (3) the exploration of saturated and unsaturated fatty acids in the initiation of polyketide biosynthesis; (4) the inhibition of aflatoxin biosynthesis at the prebisfuran stage; (5) the investigation of radical pathways to rearrangement of the averufin side chain; (6) the initiation of cell-free studies of key conversions in the pathway; (7) the continued generation of blocked mutants of A. parasiticus and characterization of new metabolites; (8) the total synthesis of aryldihydrobisfurans for the purpose of labeling experiments and total syntheses of aflatoxin B1 and sterigmatocystin.
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