Biosynthesis of the Hypotensive Metabolite Oudenone by Oudemansiella radicata. 1. Intact Incorporation of a Tetraketide Chain Elongation Intermediate

Article abstract of DOI:10.1021/jo00126a050

The biosynthesis of the fungal metabolite oudenone (1) was investigated in cultures of Oudemansiella radicata.Feeding experiments using 13C- and 2H-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 13C-labeled acetate.Labeling of oudenone (1) from <1,4-13C2>succinate or L-<5-13C>glutamic acid was not observed, whereas the pattern of 13C labeling from <2,3-13C2>succinate was identical to that observed with <1,2-13C2>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.