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

Sequence analysis of the dnrR(2) locus from the cluster of daunorubicin 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 protein on the basis of conservation of the deduced amino acid sequence relative to those of known response regulators and the properties of the dnrN::aphII mutant. Surprisingly, amino acid substitutions (glutamate and 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 glaucescens tetracenomycin C resistance gene repressor (TcmR) and to two Escherichia coli repressors, the biotin operon repressor (BirA) and the tetracycline resistance gene repressor (TetR), The dnrN::aphII mutation was suppressed by introduction of the dnrI gene on a plasmid. Since the introduction of dnrN failed to restore antibiotic production to a dnrI::aphII mutant, these data suggest the presence of a regulatory cascade in which dnrN activates the transcription of dnrI, which in turn activates transcription of the daunorubicin biosynthesis genes.