The proposed mechanism of P-450 inhibitors possessing heteroaromatics suggests that these chemicals might block a wide range of oxidation steps in biosynthesis of secondary metabolites. This possibility was examined for the following three natural products. 1. Chaetoglobosin A (1): Treatment of Chaetomium subaffine with metyrapone caused the accumulation of three plausible intermediates, named as prochaetoglobosin I (2), II (3) and III (4). Their structures including relative configuration were determined by spectroscopic methods. On the basis of incorporation experiment with [1-^<13>C, ^<18>O_2]sodium acetate, origin of oxygen atoms at C-1 and C-23 of 1 was established. These data allow us to propose the biosynthetic pathway of 1. 2. Aphidicolin (5): Late biosynthetic stage of tetrahydroxyditerpene, aphidicolin (5) was investigated. The possible precursors, 3, 17, 18-trideoxyaphidicolin (6) and 3-deoxyaphidicolin (7) were found in the culture, in which inhibitor was added. The structures were identified by comparison of the authentic samples from either natural or synthetic.The conversion of ^<14>C-labeled 6 to 5 and to 7 was achieved under the conditions with and without inhibitor. 3. Nigericin (10): The oxidation sequence of 10 was examined by the inhibitor experiment. Identification of grisorixin (11) from the medium treated with inhibitor suggests that 30-hydroxylation occurred at final step.
