prodigiosin and metacycloprodigiosin

Covering: up to the end of 2017 The roles played by Rieske non-heme iron-dependent oxygenases in natural product biosynthesis are reviewed, with particular focus on experimentally characterised examples. Enzymes belonging to this class are known to catalyse a range of transformations, including oxidative carbocyclisation, N-oxygenation, C-hydroxylation and C-C desaturation. Examples of such enzymes that have yet to be experimentally investigated are also briefly described and their likely functions are discussed.

Topics: Biological Products; Cyclization; Electron Transport Complex III; Heme; Heterocyclic Compounds, 3-Ring; Hydroxylation; Oxygenases; Prodigiosin; Pyrroles; Pyrrolnitrin; Spiro Compounds

After separation of bacterial colonies on solid plates, purification, and screening through the agar cup-plate method, an antibiotic-resistant bacterial isolate was obtained, and named strain L20190601, the 16S rRNA gene sequence data of strain L20190601 to GenBank, NCBI have provided GenBank accession number MW931615. 16S rRNA gene sequencing revealed that this isolate was highly similar to a number of Streptomyces species. Among them, the homology with S. spectabilis was the highest, reaching 99.9, together with curved hyphal morphology and biochemical tests, allowed us to identify strain L20190601 as S. spectabilis. The red pigment produced by S. spectabilis strain L20190601 was structurally identified. An acid-base color reaction assay showed that when this pigment was dissolved in a solution at pH 3.0 and 9.0, the color of the solution was red and yellow, respectively. In addition, the analysis of absorption spectra revealed that at pH 8.0 and 3.0, the maximum absorption peaks were at 466 and 531 nm, respectively. These results are consistent with the spectral absorption characteristics of metacycloprodigiosin reported in the literature. Moreover, the retention time of purified pigments was identical to those of standard metacycloprodigiosin solutions. Mass spectrometry analysis revealed that the molecular weight of the red compound was 392.2 [M + H]

Topics: Anti-Bacterial Agents; Arthrodermataceae; Microbial Sensitivity Tests; Prodigiosin; RNA, Ribosomal, 16S; Soil Microbiology; Streptomyces

Ion mobility spectrometry was utilized to corroborate the identity of streptorubin B (

Topics: Biological Products; Ion Mobility Spectrometry; Molecular Structure; Prodigiosin; Streptomyces coelicolor

The aim of the study is the research and identification of a Streptomyces strain as a new producer of spectinabilin, undecylprodigiosin and metacycloprodigiosin. Among 54 actinomycete isolates isolated from El-Ogbane forest soils in Algeria, only one isolate, designated V

Topics: Algeria; Anti-Infective Agents; Antioxidants; DNA, Bacterial; Fatty Acids; Forests; Phylogeny; Prodigiosin; Pyrones; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Soil Microbiology; Streptomyces

Topics: Apoptosis; beta Catenin; Cell Line, Tumor; Humans; Mutation; Prodigiosin; Vacuolar Proton-Translocating ATPases

A merged conjugate addition/oxidative coupling sequence that represents an efficient strategy for preparing structurally diverse pyrroles has been developed. Success of the method hinged upon the controlled oxidative coupling of unsymmetrical silyl bis-enol ether intermediates, formed by the 1,4-addition of a Grignard reagent with subsequent enolate trapping by a (chloro)silylenol ether. The process was applied to the first enantioselective syntheses of the biologically active pyrrolophane natural products, metacycloprodigiosin and prodigiosin R1.

Topics: Oxidation-Reduction; Prodigiosin; Stereoisomerism

Bioassay-guided fractionation of CHCl3 extract from the fermentation broth of a sponge Mycale plumose-derived actinomycete Saccharopolyspora sp. nov., led to the isolation of two known prodigiosin analogs--metacycloprodigiosin (1) and undecylprodigiosin (2). These compounds exhibited significant cytotoxic activities against five cancer cell lines: P388, HL60, A-549, BEL-7402, and SPCA4. This is the first report on the significant cytotoxicity of metacycloprodigiosin (1) against human cancer cell lines.

Topics: Animals; Antineoplastic Agents; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemical Fractionation; Chloroform; HL-60 Cells; Humans; Mice; Molecular Structure; Pigments, Biological; Porifera; Prodigiosin; Saccharopolyspora

Bioassay-guided fractionation of the extract from the fermentation broth of Streptomyces spectabilis BCC 4785 led to the isolation of three principle antimalarial agents, metacycloprodigiosin, bafilomycin A(1), and spectinabilin. Metacycloprodigiosin exhibited potent in vitro activity against Plasmodium falciparum K1, with a 50% inhibitory concentration of 0.0050 +/- 0.0010 microg/ml, while its cytotoxicity was much weaker.

Topics: Animals; Antimalarials; Fermentation; Plasmodium falciparum; Prodigiosin; Soil Microbiology; Streptomyces

We reported previously (Kataoka, T., Muroi, M., Ohkuma, S., Waritani, T., Magae, J., Takatsuki, A., Kondo, S., Yamasaki, M., and Nagai, K. (1995) FEBS Lett. 359, 53-59) that prodigiosin 25-C uncoupled vacuolar H+-ATPase, inhibited vacuolar acidification, and affected glycoprotein processing. In the present study we show that prodigiosins (prodigiosin, metacycloprodigiosin, and prodigiosin 25-C) inhibit the acidification activity of H+-ATPase chloride dependently, but not membrane potential formation or ATP hydrolysis activity, and suggest that they promote H+/Cl- symport (or OH-/Cl- exchange, in its equivalence) across vesicular membranes. In fact, prodigiosins displayed H+/Cl- symport activity on liposomal membranes. First of all, they decreased the internal pH of liposomes depending on the external chloride, and raised it depending on the internal chloride when external buffer was free from chloride. Second, their effect was electroneutral and not seriously affected by the application of an inside positive membrane potential generated by K+ and valinomycin. Finally, they promoted the uptake of [36Cl] from external buffers with concomitant intraliposomal acidification when external pH was acidic relative to liposome interior. As prodigiosins hardly inhibit the catalytic activity (ATP hydrolysis) unlike well known OH-/Cl- exchangers (for example, tributyltin chloride), they should provide powerful tools for the study of molecular machinery and cellular activities involving transport of protons and/or chloride.

Topics: Animals; Antiporters; Chlorides; Hydrogen; Hydroxides; Liposomes; Lysosomes; Prodigiosin; Proton Pumps; Proton-Translocating ATPases; Rats; Vacuolar Proton-Translocating ATPases

We reported previously [Kataoka, Muroi, Ohkuma, Waritani, Magae, Takatsuki, Kondo, Yamasaki and Nagai (1995) FEBS Lett. 359, 53-59] that prodigiosin 25-C (one of the red pigments of the prodigiosin group produced by micro-organisms like Streptomyces and Serratia) uncoupled vacuolar H+-ATPase, inhibited vacuolar acidification and affected glycoprotein processing. In the present study we show that prodigiosin, metacycloprodigiosin and prodigiosin 25-C, all raise intralysosomal pH through inhibition of lysosomal acidification driven by vacuolar-type (V-)ATPase without inhibiting ATP hydrolysis in a dose-dependent manner with IC50 values of 30-120 pmol/mg of protein. The inhibition against lysosomal acidification was quick and reversible, showing kinetics of simple non-competitive (for ATP) inhibition. However, the prodigiosins neither raised the internal pH of isolated lysosomes nor showed ionophoric activity against H+ or K+ at concentrations where they strongly inhibited lysosomal acidification. They required Cl- for their acidification inhibitory activity even when driven in the presence of K+ and valinomycin, suggesting that their target is not anion (chloride) channel(s). In fact, the prodigiosins inhibited acidification of proteoliposomes devoid of anion channels that were reconstituted from lysosomal vacuolar-type (V-)ATPase and Escherichia coli phospholipids. However, they did not inhibit the formation of an inside-positive membrane potential driven by lysosomal V-ATPase. Instead, they caused quick reversal of acidified pH driven by lysosomal V-ATPase and, in acidic buffer, produced quick acidification of lysosomal pH, both only in the presence of Cl-. In addition, they induced swelling of liposomes and erythrocytes in iso-osmotic ammonium salt of chloride but not of gluconate, suggesting the promotion of Cl- entry by prodigiosins. These results suggest that prodigiosins facilitate the symport of H+ with Cl- (or exchange of OH- with Cl-) through lysosomal membranes, resulting in uncoupling of vacuolar H+-ATPase.

Topics: Adenosine Triphosphate; Animals; Antiporters; Chlorides; Erythrocytes; Humans; Hydrogen; Hydrogen-Ion Concentration; In Vitro Techniques; Ion Transport; Kinetics; Lysosomes; Male; Prodigiosin; Proteolipids; Proton-Translocating ATPases; Rats; Rats, Wistar; Uncoupling Agents; Vacuolar Proton-Translocating ATPases

Prodigiosin 25-C and metacycloprodigiosin were found to suppress PTH-stimulated pit formation by cultured osteoclasts on bone slices. They also inhibited the acidification of vacuolar organelles in intact osteoclastic cells. Since the acidic pH in these organelles is generated by the action of proton-pumping ATPases of the organelle, these results indicate that the proton-pumping activity of V-ATPase in osteoclastic cells is essential in bone resorption and that the inhibition of the acidification of vacuolar organelles by prodigiosins results in suppression of PTH-stimulated bone resorption.

Topics: Animals; Bone Resorption; Cells, Cultured; Molecular Structure; Osteoblasts; Prodigiosin; Rats; Rats, Sprague-Dawley

Metacycloprodigiosin is an antibiotic that has been shown to suppress T-cell proliferation induced by concanavalin A in vitro. We examined the effect of metacycloprodigiosin on murine allogenic skin and heart transplantation models, and compared graft rejection with donor-specific cytotoxic T-cells and antibody activity. The antibiotic slightly prolonged the survival of C57Bl/6 heart and skin grafts in BALB/c mice, although the effect was less that that of cyclosporin A. The effect was more evident in Bm1 (H-2D mutant) skin grafts on C57B1/6 hosts or in a minor histocompatibility antigen-mismatched model. In contrast, metacycloprodigiosin suppressed anti-graft cytotoxic T-cell activity of BALB/c spleen grafted with C57B1/6 skin as comparable to cyclosporin A, but had only partial effect on antibody production. Thus, metacycloprodigiosin is more effective in reducing splenic cytotoxic T-cell activity than in prolonging murine skin or cardiac allografts.

Topics: Animals; Cyclosporine; Female; Graft Survival; Heart Transplantation; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Prodigiosin; Skin Transplantation; T-Lymphocytes, Cytotoxic