prodiginine and undecylprodigiosin

Prodiginines are bacterial red polypyrrole pigments and multifaceted secondary metabolites. These agents have anti-proliferative, immunosuppressive, antimicrobial, and anticancer effects. Recent analysis revealed that prodigiosin hypersensitizes Serratia marcescens to gamma radiation. In the present study, we report the cytotoxicity and genotoxicity properties of undecylprodigiosin and butylcycloheptylprodigiosin in the presence and absence of radiation through the MTT and alkaline comet experiments.. Findings demonstrated that undecylprodigiosin was at least a fivefold more cytotoxic at low radiation doses (1 and 3 Gy) on both MCF7 and HDF lines rather than in the absence or high radiation doses (5 Gy) (P value < 0.05). Although butylcycloheptylprodigiosin toxicity on MCF7 and HDF was dose-dependent, it was not influenced by any radiation doses (P value > 0.05). Comet findings confirmed that these compounds' genotoxicity is only dose-dependent. Radiation had no significant effects on DNA damage on any of the cells (P value > 0.05).. In general, it can be concluded that the prodiginines are cytotoxic agents that act as a double-edged sword, radiosensitizers and radio-protective, respectively at low and high radiation doses in cancer treatment process. As the results they could be used in antitumor therapies very soon.

Topics: Anti-Infective Agents; Antineoplastic Agents; Cell Line; DNA Damage; Humans; Immunosuppressive Agents; MCF-7 Cells; Neoplasms; Photosensitizing Agents; Prodigiosin

Gram-positive

Topics: Anti-Bacterial Agents; Base Composition; Base Sequence; DNA Transposable Elements; Gene Expression Regulation, Bacterial; Gene Library; Mutagenesis, Insertional; Prodigiosin; Secondary Metabolism; Streptomyces coelicolor; Transposases

The last step of proline biosynthesis is typically catalysed by the enzyme Δ(1)-pyrroline-5-carboxylate reductase, encoded by the proC gene. Complete genome sequencing of Streptomyces coelicolor, a soil-dwelling Gram-positive bacterium that uses proline as a precursor for synthesis of prodiginine, revealed a single copy of this gene. Unexpectedly, disruption of this proC homologue (Sco3337) in S. coelicolor M145 yielded a prototrophic strain, yet the reductase activity of Sco3337 was confirmed by complementation of an Escherichia coli proC mutant. Multicopy proC within different genetic contexts elicited a transient production of prodiginines, which showed differential production kinetics of the two most common forms of this natural product produced by S. coelicolor, i.e. streptorubin B (cyclic) and undecylprodigiosin (linear). The metabolic and evolutionary implications of these observations are discussed.

Topics: Biological Evolution; delta-1-Pyrroline-5-Carboxylate Reductase; Gene Dosage; Genes, Bacterial; Mutation; Prodigiosin; Proline; Pyrroline Carboxylate Reductases; Streptomyces coelicolor