Intrinsic limitations on the continued production of the antibiotic patulin by Penicillium urticae.

The initial cause of the cessation of patulin biosynthesis in submerged cultures of Penicillium urticae was sought. The extrinsic limitations to patulin biosynthesis in fermentor cultures were successfully removed and kinetic profiles of the metabolites of the pathway and of three pathway enzymes were determined over a 60-h period. These profiles indicated that the first intrinsic limitation involved a decrease in the cellular content of the first enzyme of the pathway, 6-methylsalicylic acid synthetase. Other enzyme contents also decreased but on a significantly longer time scale. Thus the in vivo half-maximal lifetimes for the synthetase and for the m-hydroxybenzyl alcohol and isoepoxydon dehydrogenases were about 7, 17, and 19 h, respectively.