A functional study of the global transcriptional regulator PadR from a strain Streptomyces fradiae‐nitR+bld, resistant to nitrone‐oligomycin

Abstract

We describe Streptomyces fradiae mechanisms of sensitivity to nitrone-oligomycin A, a derivative of oligomycin A. We obtained S. fradiae-nitR bld, a nitrone-oligomycin A resistant mutant with a «bald» phenotype. Comparative genomic analysis of the wild-type S. fradiae ATCC19609 and S. fradiae-nitR bld revealed a mutation in padR - a gene encoding a multifunction transcription regulator, which resulted in the amino acid replacement in a highly conserved DNA-binding domain. Bioinformatics genome analysis of S. fradiae ATCC19609 discovered a PadR binding site 13 bp upstream the start codon of the marR transcription factor gene. Induction of S. fradiaenitR bld and w.t. strains with nitrone-oligomycin A lead to a significant increase in expression level of the marR gene in the w.t. strain, but no change observed in mutant strain. We identified differences between DNA-protein interactions of the mutant and native PadR proteins with its putative binding site in S. fradiae ATCC19609. This allowed us to suggest that the padR gene, that harbored a single nucleotide mutation in the S. fradiaenitR bld strain, might be involved in the mechanism of resistance to nitrone-oligomycin A. We assume the participation of the transcriptional factorpadR in the formation of the bald phenotype.

Effect of the TetR family transcriptional regulator Sp1418 on the global metabolic network of Saccharopolyspora pogona

“…Currently, a substantial number of proteins have been reported to regulate the metabolites of bacteria [10][11][12], including some global regulators [13,14], which are of great significance in growth, phenotype and metabolism. TetR family regulators have been reported in numerous organisms [15,16]; they are involved in the regulating biosynthesis of antibiotics, efflux pumps, osmotic stress, etc., and typically function as repressors [17] to regulate the expression of genes, such as the ameABC operon [18] and fadR operator [19].…”

A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate

“…It has been reported that FA can trigger dissociation of the phenolic acid decarboxylase regulator (PadR) repressor, a transcriptional regulator of the padA gene in Bacillus subtilis 168, from its specific DNA binding sequence O PadR ( 34 , 35 ). On the basis of this switchable molecular interaction, we propose to construct a novel genetic switch in which PadR is fused to eukaryotic epigenetic effector domains.…”

Synthesis and Biological Activity of 7(7,11)-Hydroderivatives of Oligomycin A

“…Полусинтетические производные олигомицина А также позволили выявить ряд новых внутриклеточных мишеней для химиотерапии. [9,10] Ранее было описано неселективное восстановление кетогрупп в 7 и 11 положении олигомицина D и смеси олигомицинов А, В и С действием NaBH 4 в спирте. [11] Биохимические исследования смеси энантиомеров 7-дигидро-и 7,11-тетрагидроолигомицина D показали, что восстановленные производные сохранили способность к ингибированию АТФ-синтазы.…”

“…Also, semi-synthetic oligomycin A derivatives are useful tools for molecular genetic studies of additional targets for this family of antibiotics. [9,10] Previously Ramirez F. et al have described the reaction of oligomycins with sodium borohydride resulting in mixture of diastereomeric 7-dihydro-and 7,11-tetrahydro derivatives without further separation and characterization of individual products. [11] Also, there is no data on biological activity of these reduced oligomycins against fungal/actinomycetes strains and tumor cell lines in article mentioned above.…”