Reversal of Chlorination Inhibitors in Streptomyces aureofaciens

Abstract

A NUMBER of compounds related to antithyroid agents have been used as chlorination inhibitors to cause Streptomyces aureofaciens to produce tetracycline rather than the normally predominant chlortetracycline^1–3. The action of these inhibitors is reversed to some extent by Cu⁽⁺⁺⁾ and Ag⁽⁺⁺⁾ (ref. 3). Sekizawa has reported⁴ that chloro-propanediols also reverse the effect of these chlorination inhibitors and suggested that this reversal is due to the incorporation of the 3-C chlorinated unit into the bio-synthetic pathway at some point prior to the chlorination step. Such an explanation is not consistent with recent evidence that the tetracyclines are built up by the head-to-tail linkage of polyacetate or polymalonate units^5–7. In the present communication we wish to offer an alternative explanation for the action of chloropropanediol in reversing the effect of chlorination inhibitors.