Disease relevance of C02811

• Isolation of pure anhydrotetracycline oxygenase from Streptomyces aureofaciens [1].
• The analogs tested, chelocardin, anhydrotetracycline, 6-thiatetracycline, anhydrochlortetracycline, and 4-epi-anhydrochlortetracycline, were bactericidal and caused the lysis of Escherichia coli accompanied by the release of the cytoplasmic enzyme beta-galactosidase into the supernatant [2].
• Addition of anhydrotetracycline led to a 62-fold induction of GFP expression in vitro and 15-fold induction in a mouse mycobacterial peritonitis model in the presence of maximal tetR expression [3].
• We have placed the constitutively expressed hprK in its native chromosomal locus under anhydrotetracycline-dependent transcriptional control to establish the correlation between HPrK/P amounts and the efficiency of CCR in Bacillus subtilis [4].
• We report the development of mycobacterial gene regulation systems that allow controlling gene expression in fast and slow-growing mycobacteria, including Mycobacterium tuberculosis, using anhydrotetracycline (ATc) as inducer [5].

High impact information on C02811

• Expression of HER-2 could be down-regulated below detection limit (>625-fold dilution) by exposure of NIH3T3-her2 cells to anhydrotetracycline (ATc) [6].
• The otcC gene encodes an anhydrotetracycline oxygenase that catalyzes a hydroxylation of the anthracycline structure at position C-6 after biosynthesis of the polyketide backbone is completed [7].
• The novel promoter PLtetO-1 allows the regulation of gene expression over an up to 5000-fold range with anhydrotetracycline (aTc) whereas with IPTG and arabinose the activity of Plac/ara-1 may be controlled 1800-fold [8].
• The extent of this recovery is attenuated markedly when transcription of the recombinant AT1-R gene is suppressed by cotreatment of the cells with anhydrotetracycline [9].
• The mutations were isolated on multicopy Tn10 tet plasmids by selecting for resistance to the inducer 5a,6-anhydrotetracycline [10].

Chemical compound and disease context of C02811

• Differences between E. coli K-12 backgrounds influence the tetracycline and anhydrotetracycline sensitivity of multicopy strains; ZnCl2 enhances the tetracycline and anhydrotetracycline sensitivity of these strains two- to threefold [11].
• The localization of anhydrotetracycline oxygenase and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) was studied by determining the enzyme activities in subcellular fractions obtained by differential centrifugation of the mycelia of Streptomyces aureofaciens after lysozyme treatment [12].
• Subcellular localization of enzymes in Streptomyces aureofaciens and its alteration by benzyl thiocyanate. II. Anhydrotetracycline oxygenase and glucose-6-phosphate dehydrogenase [12].

Biological context of C02811

• After introduction of the construct into E. coli and induction with anhydrotetracycline, overexpression of ftsZ(Bbu) generated a filamentous phenotype [13].
• The anhydrotetracycline (ATC) oxygenase enzyme which carries out the conversion of ATC to dehydrotetracycline was purified and the N-terminal amino acid sequence was determined [14].
• The investigation was concentrated on the subject of the kinetics of the epimerization of anhydrotetracycline to 4-epianhydrotetracycline in acetate buffer [15].
• Biosynthesis of the F(ab) fragment in a high cell density fermenter was induced by addition of anhydrotetracycline [16].

Anatomical context of C02811

• This increased binding is in contrast to the lower antibiotic activity of anhydrotetracycline and indicates that the Tet repressor and ribosomes recognize the drug differently [17].
• The experimental evidence was based on the assay of anhydrotetracycline oxygenase in subcellular fractions, ultracytochemical localization and electron-probe X-ray microanalysis of the product in the mycelium [18].

Associations of C02811 with other chemical compounds

• A second class of analogs tested, including chelocardin, anhydrotetracycline, 6-thiatetracycline, anhydrochlortetracycline, and 4-epi-anhydrochlortetracycline, failed to inhibit protein synthesis in vitro or were very poor inhibitors [19].
• TetR H100A and E147A are induced by atc, with and without Mg(2+), showing 110-fold and 1000-fold decreased Mg(2+)-dependent and unchanged Mg(2+)-independent atc binding, respectively [20].
• All of these Atr mutations are located in the Tn10 tet region; the majority (18 of 20) have no effect on tetR repressor function [21].
• We have analyzed the tryptophan (trp) fluorescence-decay kinetics of single trp mutants of the Tet repressor protein in the free, the tet operator and anhydrotetracycline (atc)-bound states [22].
• Association kinetics reveal different recognition of these TetR variants by anhydrotetracycline, but the binding constants indicate similar stabilization [23].

Gene context of C02811

• Addition of the inducer 5a,6-anhydrotetracycline results in a 270- to 430-fold increase in tetA mRNA and a 35- to 65-fold increase in tetR mRNA [24].
• Some Atr mutations reduce expression of the tetA gene by altering either the tetR repressor or the tetA promoter [21].
• IS insertions that result in an Atr Tcs phenotype are clustered in a 150-base-pair promoter-proximal region of the tetA resistance gene [21].
• After induction by anhydrotetracycline, expression of antisense ftsZ RNA resulted in generation of filamentous B. burgdorferi that were unable to divide and grew more slowly than uninduced cells [13].
• The Mg(2+)-free binding of atc to TetR leads to induction in vitro, demonstrating that the metal is not necessary to trigger the associated conformational change [20].

Analytical, diagnostic and therapeutic context of C02811

• The ability to induce the expression of green fluorescent protein after treatment by anhydrotetracycline in the same transformants was also analyzed [25].
• Anhydrotetracycline oxygenase was purified both by affinity chromatography and by hydrophobic interaction chromatography [26].
• Molecular weight of anhydrotetracycline oxygenase was determined to be 115,000 by Sephadex G-200 gel filtration [26].
• This paper describes the high performance liquid chromatographic (HPLC) analysis of eight parent tetracycline standards: tetracycline, chlortetracycline, rolitetracycline, oxitetracycline, minocycline, doxycycline, democlocycline, methacycline; and three tetracycline epimers: epitetracycline, epianhydrotetracycline, and anhydrotetracycline [27].

References