Decarestrictine A1

The structures of the novel 10-membered lactones, named decarestrictines A1/A2 (1/2), B (3), C1/C2 (5/6) and D (7), are presented. The structures of these secondary metabolites, isolated from different Penicillium species, were established by spectroscopic analysis and confirmed by X-ray analysis of 7 and a derivative of 3 leading to the stereochemical information. The decarestrictines vary in the oxygenation pattern between C-3 and C-7 and show structural similarities to known lactones from other fungi.

In the late biosynthesis of the decarestrictines, inhibitors of the de novo formation of cholesterol isolated from the culture broth of Penicillium simplicissimum (FH-A 6090), a common pentaketide precursor undergoes post-polyketide modifications leading to the different members of the decarestrictine family. Besides subsequent enzymatically catalyzed reactions an unexpected non-enzymatic conversion was found to be the key step in the biosynthetic sequence. Under acidic conditions during fermentation the decarestrictines A1 and A2 (3 and 4) are converted into the main product decarestrictine D (2) and the new decarestrictines N (5) and O (6), whose physico-chemical data are reported. Mechanistic aspects of the non-enzymatic reaction as well as a more detailed picture of the biosynthetic relationships of the decarestrictine family are described. By the application of pH-static fermentations these results were successfully used to manipulate the secondary metabolite pattern of strain FH-A 6090 directing the fermentation process to produce desired members of the decarestrictine family.