BIOSYNTHESIS OF THE HYPOTENSIVE METABOLITE OUDENONE BY OUDEMANSIELLA-RADICATA .1. INTACT INCORPORATION OF A TETRAKETIDE CHAIN ELONGATION INTERMEDIATE

The biosynthesis of the fungal metabolite oudenone (1) was investigated in cultures of Oudemansiella radicata. Feeding experiments using C-13 and H-2-labeled precursors, as well as NMR analyses of the labeled metabolite, suggested a polyketide origin. The incorporation of six acetate units into the carbon skeleton of 1 was observed when cultures were fed the N-acetylcysteamine thioester derivative of C-13-labeled acetate. Labeling of oudenone (1) from [1,4-C-13(2)]succinate or L-[5-C-13]-glutamic acid was not observed, whereas the pattern of C-13 labeling from [2,3-C-13(2)]succinate was identical to that observed with [1,2-C-13(2)]acetate. The proposed advanced intermediate (5S)-5-hydroxyoctanoic acid (2) was synthesized as the deuterium labeled N-acetylcysteamine thioester derivative (S)-19 and successfully incorporated into 1. A biosynthetic scheme and cyclization mechanism, consistent with the experimental data, is proposed.