Biosynthetic studies on the decarestrictine family

Feeding experiments with sodium [13C]-labelled acetates and [2-13C]-malonic acid to Penicillium simplicissimum(strain FH-A 6090) proved the polyketide origin of the ten-membered lactones of the decarestrictines. The oxygenation pattern was investigated by incorporation studies with sodium [1 -13C, 18O2]-acetate and [18O2]-gas, resulting in a detailed biosynthetic analysis of the main products decarestrictine B, 1, and D, 2. The various decarestrictines seem to arise from a common pentaketide precursor, which undergoes subsequent post-polyketide synthase modifications. In combination with further experiments (e.g. product profiles during fermentation, pH-static fermentations) their biosynthetic relationships are described. These results were used to manipulate the metabolite pattern of strain FH-A 6090 directing the fermentation process to produce the desired decarestrictines.