The biosynthesis of the fungal metabolite oudenone ( 67 ) was investigated. The Ì-diketone ( 70 ) was synthesized and shown to be the open-chain biosynthetic precursor of oudenone. Intact incorporation of 70 into 67 was achieved upon incubation of 2 H-labeled, N -acetylcysteamine thioester derivative of 70 with growing cultures of Oudemansiella radicata . The proposed mechanism for the cyclization of 70 into 67 is analogous to the "polyepoxide cascade" model, which has been previously implicated in the biosynthesis of polyether antibiotics.*  The antitumor metabolite verucopeptin ( 89 ) is structurally characterized by a polyketide-derived tetrahydropyranyl side chain and a 19-membered cyclodepsipeptide. A DNA fragment of 72.5 kb was isolated from a cosmid library of Actinomadura verrucosospora chromosomal DNA. Partial analysis and sequencing of this gene cluster revealed the presence of several open reading frames (ORFs) coding for modular polyketide synthase (PKS) type I enzymes and multifunctional, non-ribosomal peptide synthetase enzymes (NRPS). Based on the chemical structure of verucopeptin, the enzymatic motifs identified are consistent with those expected to be associated with its biosynthesis. A gene disruption experiment was performed with A. verrucosospora in order to demonstrate that the cloned 72.5 kb DNA fragment is associated with the biosynthesis of verucopeptin.*  *Please refer to dissertation for diagrams