REGULATION OF DAUNORUBICIN PRODUCTION IN STREPTOMYCES-PEUCETIUS BY THE DNRR(2) LOCUS

Sequence analysis of the dnrR(2) locus from the cluster of daunorubici n biosynthesis genes in Streptomyces peucetius ATCC 29050 has revealed the presence of two divergently transcribed open reading frames, dnrN and dnrO. The dnrN gene appears to encode a response regulator protei n on the basis of conservation of the deduced amino acid sequence rela tive to those of known response regulators and the properties of the d nrN::aphII mutant. Surprisingly, amino acid substitutions (glutamate a nd asparagine) at the putative site of phosphorylation (aspartate 55) resulted in a reduction rather than a complete loss of DnrN activity, The deduced DnrO protein was found to be similar to the Streptomyces g laucescens tetracenomycin C resistance gene repressor (TcmR) and to tw o Escherichia coli repressors, the biotin operon repressor (BirA) and the tetracycline resistance gene repressor (TetR), The dnrN::aphII mut ation was suppressed by introduction of the dnrI gene on a plasmid. Si nce the introduction of dnrN failed to restore antibiotic production t o a dnrI::aphII mutant, these data suggest the presence of a regulator y cascade in which dnrN activates the transcription of dnrI, which in turn activates transcription of the daunorubicin biosynthesis genes.