THE BIOSYNTHESIS OF ANTIBIOTIC F-244 IN FUSARIUM SP ATCC-20788 - ORIGIN OF THE CARBON, HYDROGEN, AND OXYGEN-ATOMS

Biosynthetic incorporation experiments were performed with carbon-13 l abelled precursors including sodium [1-C-13]-, [2-C-13], and [1,2-C-13 (2)]-acetate as well as [methyl-C-13]methionine into antibiotic F-244 (1) in growing cultures of Fusarium sp. ATCC 20788. After conversion t o the methyl ester 2, analysis by NMR showed that the carbon skeleton of 1 derives from seven intact acetate units; the remaining four carbo ns are from methionine. Hence, the pathway is similar to that reported for 1 in Scopulariopsis. The biogenesis of the hydrogen atoms in 1 wa s also investigated. Incorporation of sodium [1-C-13,O-18(2)]acetate g ives 2, which exhibits O-18-induced isotope shifts at C-1 and C-3. The labelling pattern is consistent with formation of the beta-lactone ri ng by nucleophilic attack of a C-3 hydroxyl group in the nascent polyk etide precursor onto the C-l carbonyl.