Effect of chloramphenicol on its biosynthesis by Streptomyces species 3022a

Measurements of (3H) chloramphenicol production in cultures of Streptomyces species 3022a grown on a medium containing (6-3H) D-glucose and (3-14C) chloramphenicol showed that chloramphenicol inhibits its own biosynthesis. Similar results were obtained in cultures supplemented with the antibacterial p-methylthio- analogue of chloramphenicol. Here synthesis of the antibiotic was completely suppressed until the concentration of analogue had been reduced by inactivating enzymes. In contrast, the L-threo- and p-methylsulfonyl- analogues did not delay growth of the organism and had little effect on chloramphenicol biosynthesis. However, like chloramphenicol and its p-methylthio- analogue, the L-threo and p-methylsulfonyl compounds were degraded. Degradation of chloramphenicol and the p-methylsulfonyl-analogue ceased when endogenously produced antibiotic reached a concentration of 10–30 mg/liter, suggesting that changes in cell permeability are associated with the onset of chloramphenicol synthesis.