Regulation of enzymes involved in the biosynthesis of the sesquiterpene antibiotic pentalenolactone in Streptomyces arenae.

The production of the sesquiterpenoid antibiotic pentalenolactone in the producer strain Streptomyces arenae TU 469 is controlled by the activity of the enzyme farnesylpyrophosphate cyclase. In contrast to the activity of this enzyme, the specific activities of all other enzymes of the mevalonoid pathway tested so far, proved to be not rate-limiting. Several metabolites of the pentalenolactone pathway were tested for inhibitory effects on the activity of the HMG-CoA reductase and farnesylpyrophosphate cyclase. The activity of the cyclase was inhibited by low concentrations of pentalenolactone and its derivatives, thus suggesting an end product inhibition of the starting enzyme of the pentalenolactone pathway. The activity of HMG-CoA reductase was not inhibited by pentalenene or any pentalenolactone-derivatives. According to these results, an end-product inhibition of the first enzyme which is specific for pentalenolactone synthesis seems to be a mechanism involved in the regulation of pentalenolactone biosynthesis.