BLDA DEPENDENCE OF UNDECYLPRODIGIOSIN PRODUCTION IN STREPTOMYCES-COELICOLOR A3(2) INVOLVES A PATHWAY-SPECIFIC REGULATORY CASCADE

The production of the red-pigmented tripyrrole antibiotic undecylprodi giosin (Red) by Streptomyces coelicolor A3(2) depends on two pathway s pecific regulatory genes, redo and redZ. Redo is homologous to several other proteins that regulate antibiotic production in streptomycetes; RedZ is a member of the response regulator family. redZ transcripts w ere detected during exponential growth and increased in amount during transition and stationary phases; transcription of redo was confined t o the two latter stages of growth. Whereas mutation of redo had no eff ect on redZ transcription, transcription of redo was highly dependent on redZ, suggesting that RedZ is a transcriptional activator of redD. bldA, which encodes the only tRNA of S. coelicolor that can efficientl y translate the rare leucine codon UUA, is required for Red production at higher phosphate concentrations, While the redD transcript contain s no UUA codons, the redZ mRNA contains one. Transcription of redZ app eared to be unaffected in a bldA mutant; in contrast, redo transcripti on was undetectable, consistent with the translational dependence of r edZ on bldA and the transcriptional dependence of redo on redZ. Red pr oduction in a bldA mutant was restored by multiple copies of redZ, pre sumably reflecting a low level of mistranslation of the redZ UUA codon , while multiple copies of redD had no effect, presumably a consequenc e of the severe dependence of redo transcription on RedZ. Transcriptio n of redZ appears to be negatively autoregulated.