prodigiosin and roseophilin

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

The pyrrole alkaloids of the prodigiosin family make up an unusual chapter in the chemistry of natural products. Owing to the characteristic red color of these secondary metabolites, colonies of the Gram-negative-producing bacteria may strikingly resemble droplets of blood. This phenomenon caused considerable confusion in the past and was likely responsible for many seemingly miraculous (prodigious) events. After the eventual transition from superstition to science, the prodigiosins started to attract considerable attention because of their promising physiological properties. Most interesting are the immunosuppressive activities at doses that are not cytotoxic, in particular since in vivo studies suggest that the prodigiosins act synergistically with cyclosporine A or FK 506, which are presently the dominant drugs in clinical immunosuppressive regimens. Furthermore, the chemistry of the closely related and structurally rather unique alkaloid roseophilin is summarized, a cytotoxic agent that recently became the focal point of many innovative total syntheses.

Topics: Alkaloids; Animals; Anti-Infective Agents; Heterocyclic Compounds, 3-Ring; History, 16th Century; History, 19th Century; History, 20th Century; History, Ancient; History, Medieval; Humans; Molecular Structure; Prodigiosin; Pyrroles

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Gene Expression Regulation, Bacterial; Heterocyclic Compounds, 3-Ring; Humans; Molecular Structure; Multigene Family; Prodigiosin; Pyrroles; Streptomyces coelicolor

Streptomyces griseoviridis 2464-S5 produces prodigiosin R1, a tripyrrole antibiotic, and roseophilin, a structurally related compound containing two pyrrole and one furan rings. A gene cluster for the biosynthesis of a prodigiosin was identified in S. griseoviridis. The cluster consisted of 24 open reading frames, including 21 genes (rphD-rphZ) homologous to prodigiosin biosynthesis genes in the red cluster in Streptomyces coelicolor A3(2). The expression of rphN in S. coelicolor lacking redN restored the production of prodigiosin.

Topics: Anti-Bacterial Agents; Blotting, Southern; Cloning, Molecular; DNA, Bacterial; Genes, Bacterial; Heterocyclic Compounds, 3-Ring; Molecular Sequence Data; Multigene Family; Open Reading Frames; Plasmids; Prodigiosin; Pyrroles; Streptomyces

Roseophilin is a unique metabolite containing two pyrrole and one furan ring and is structurally related to tripyrrole antibiotics, prodigiosins. Each homologous gene in the roseophilin producer Streptomyces griseoviridis was amplified by PCR using primers designed from the prodigiosin-biosynthesis genes redH, redM, and redW. A search for prodigiosins produced by S. griseoviridis resulted in the isolation of a new prodigiosin designated prodigiosin R1 (1). The molecular formula of 1 was established as C27H37N3O by high-resolution FABMS. The structure of 1 was elucidated by NMR spectroscopic analysis including COSY, HMQC, HMBC, and NOESY. Prodigiosin R1 (1) is a new member of the prodigiosin family possessing a cyclic alkyl side chain.

Topics: Heterocyclic Compounds, 3-Ring; Molecular Sequence Data; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Prodigiosin; Pyrroles; Streptomyces

[reaction: see text] Preparation of a cyclopentenone-fused pyrrolophane, which serves as a model for the tricyclic core of roseophilin (1), is described. The synthetic scheme features a palladium-catalyzed annulation and oxidative cleavage sequence to provide a macrocyclic ketoester (17). Modified Paal-Knorr pyrrole synthesis and Friedel-Crafts acylation complete the pyrrolophane model system (20).

Topics: Heterocyclic Compounds, 3-Ring; Ketones; Molecular Structure; Oxidation-Reduction; Prodigiosin; Pyrroles

Topics: Alkaloids; Enzyme Inhibitors; Heterocyclic Compounds, 3-Ring; Humans; Molecular Structure; Prodigiosin; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Pyrroles

Topics: Alkaloids; Anti-Bacterial Agents; DNA; Electrophoresis, Agar Gel; Heterocyclic Compounds, 3-Ring; Prodigiosin; Pyrroles; Streptomyces