Useful approach to find the plausible biosynthetic precursors of secondary metabolites using P-450 inhibitors: postulated intermediates of chaetoglobosin A

Abstract

Treatment of Chaetomium subaffine with specific cytochrome P-450 inhibitors resulted in a new generation of plausible precursors of chaetoglobosin A 1, which we have named prochaetoglobosins I 2, II 3, III 4 and IV 5, whose structures were determined by spectroscopic analysis. HPLC analysis of mycelial extract treated with the inhibitors suggest that the accumulated metabolites are precursors in the biosynthesis of compound 1. During this study, new less oxidized analogues, prochaetoglobosin IIIed6 and isochaetoglobosin J 7, were also isolated, and their structures were elucidated in a similar way.