Properties and applications of undecylprodigiosin and other bacterial prodigiosins

Stanković, Nebojša; Šenerović, Lidija; Ilić-Tomič, Tatjana; Vasiljević, Branka; Nikodinovic-Runic, Jasmina

doi:10.1007/s00253-014-5590-1

Cited by 123 publications

(118 citation statements)

References 165 publications

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“…Many peaks in the FIG 5 Relative RED production in RED-changing regulatory gene mutants and recombinants carrying the wild-type alleles. The wild-type regulatory gene alleles, including a 300-bp upstream fragment, were cloned into an integrative vector and introduced into the corresponding mutants for genetic complementation.…”

Section: Resultsmentioning

confidence: 99%

“…The genome was divided into 8,645 bins of 1 kb each in a base-by-base Tn5 transposable unit. ME, the mosaic end sequence for Tn5 transposase recognition and cutting; ori-pUC, origin for DNA replication in E. coli; aac(3)IV, apramycin resistance gene; oriT, origin for intergeneric conjugation from E. coli to S. coelicolor; bla, ampicillin resistance gene; tnp (5), the Tnp(5) gene, encoding a Tn5 transposase variant with five point mutations (E54K, M56K, L372P, P242A, and E345K). (B) Verification of randomly selected transposition mutants by Southern hybridization with the mini-Tn5 DNA probe.…”

Section: Resultsmentioning

confidence: 99%

“…1A). Besides mini-Tn5, pHL734 harbors an origin of transfer (oriT RK2 ) to initiate conjugative transfer helped by RK2-derived helper plasmids, such as pUZ8002, and a mutated Tn5 transposase gene [the Tnp (5) gene] that is codon optimized for expression in Streptomyces. Most importantly, the Tnp(5) gene was engineered to carry five point mutations (E54K, M56A, P242A, E345K, and L372P) documented to cause high transposition efficiency (37)(38)(39)(40).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, RED belongs to a group of prodiginines that exhibit a wide range of biological activities, including uses as antibacterial, antifungal, anticancer, antimalarial, and immunosuppressive agents (4,5). The biosynthetic pathway of RED has been studied extensively (6)(7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

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Large-Scale Transposition Mutagenesis of Streptomyces coelicolor Identifies Hundreds of Genes Influencing Antibiotic Biosynthesis

Wang

Chater

et al. 2017

Appl Environ Microbiol

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Gram-positive Streptomyces bacteria produce thousands of bioactive secondary metabolites, including antibiotics. To systematically investigate genes affecting secondary metabolism, we developed a hyperactive transposase-based Tn5 transposition system and employed it to mutagenize the model species Streptomyces coelicolor, leading to the identification of 51,443 transposition insertions. These insertions were distributed randomly along the chromosome except for some preferred regions associated with relatively low GC content in the chromosomal core. The base composition of the insertion site and its flanking sequences compiled from the 51,443 insertions implied a 19-bp expanded target site surrounding the insertion site, with a slight nucleic acid base preference in some positions, suggesting a relative randomness of Tn5 transposition targeting in the high-GC Streptomyces genome. From the mutagenesis library, 724 mutants involving 365 genes had altered levels of production of the tripyrrole antibiotic undecylprodigiosin (RED), including 17 genes in the RED biosynthetic gene cluster. Genetic complementation revealed that most of the insertions (more than two-thirds) were responsible for the changed antibiotic production. Genes associated with branched-chain amino acid biosynthesis, DNA metabolism, and protein modification affected RED production, and genes involved in signaling, stress, and transcriptional regulation were overrepresented. Some insertions caused dramatic changes in RED production, identifying future targets for strain improvement.IMPORTANCE High-GC Gram-positive streptomycetes and related actinomycetes have provided more than 100 clinical drugs used as antibiotics, immunosuppressants, and antitumor drugs. Their genomes harbor biosynthetic genes for many more unknown compounds with potential as future drugs. Here we developed a useful genomewide mutagenesis tool based on the transposon Tn5 for the study of secondary metabolism and its regulation. Using Streptomyces coelicolor as a model strain, we found that chromosomal insertion was relatively random, except at some hot spots, though there was evidence of a slightly preferred 19-bp target site. We then used prodiginine production as a model to systematically survey genes affecting antibiotic biosynthesis, providing a global view of antibiotic regulation. The analysis revealed 348 genes that modulate antibiotic production, among which more than half act to reduce production. These might be valuable targets in future investigations of regulatory mechanisms, for strain improvement, and for the activation of silent biosynthetic gene clusters.KEYWORDS genome-wide, transposition mutagenesis, Streptomyces coelicolor, antibiotic biosynthesis, prodiginine

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Large-Scale Transposition Mutagenesis of Streptomyces coelicolor Identifies Hundreds of Genes Influencing Antibiotic Biosynthesis

Wang

Chater

et al. 2017

Appl Environ Microbiol

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“…Recent studies put a PG family member, undecylprodigiosin pigment (UPP), in the focus of anticancer investigation based on its proapoptotic potency demonstrated in various types of tumours (20)(21)(22)(23). It has been suggested that UPP inhibits cell proliferation by inducing G2/M phase arrest and apoptosis of cancer cells.…”

mentioning

confidence: 99%

The impact of concentration and administration time on the radiomodulating properties of undecylprodigiosin in vitro

Petrović

Vasic

Mitrović

et al. 2017

Archives of Industrial Hygiene and Toxicology

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Undecylprodigiosin pigment (UPP) is reported to display cytotoxic activity towards various types of tumours. Nevertheless, its efficacy in modifying the cellular response to ionising radiation is still unknown. In this study, the radiomodulating effects of UPP were investigated. The effects of UPP were assessed in vitro by treating cultures of human peripheral blood with UPP and ionising radiation using two treatment regimens, the UPP pre-irradiation treatment and UPP post-irradiation treatment. The activity of UPP was investigated evaluating its effects on the radiation-induced micronuclei formation, cell proliferation, and induction of apoptosis. The redox modulating effects of UPP were examined measuring the catalase activity and the level of malondialdehyde, as a measure of oxidative stress. The results showed that UPP effects on cellular response to ionising radiation depend on its concentration and the timing of its administration. At low concentration, the UPP displayed radioprotective effects in γ-irradiated human lymphocytes while at higher concentrations, it acted as a radiosensitiser enhancing either mitotic catastrophe or apoptosis depending on the treatment regimen. The UPP modified redox processes in cells, particularly when it was employed prior to γ-irradiation. Our data highlight the importance of further research of the potential of UPP to sensitize tumour cells to radiation therapy by inhibiting pathways that lead to treatment resistance.

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Condensing Enzymes from Pseudoalteromonadaceae for Prodiginine Synthesis

et al. 2019

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Prodiginines are natural products that are produced by various microorganisms. As the biological activity of prodiginines varies depending on their structure, prodiginine derivatives are of interest. In order to extend the prodiginine structural diversity, new condensing enzyme homologs of PigC were analysed. The condensing enzyme PigC from S. marcescens catalyses the last step in prodiginine biosynthesis and accepts not only its natural substrate, but also synthetically produced monopyrroles. Still, the substrate spectrum of PigC is partially limited. In order to enable the biocatalytic production of new prodiginine derivatives, PigC homologs supplementing the substrate spectra of PigC are of interest. Two condensing enzymes homologs from two tambjamine producing Pseudoalteromonadaceae strains were analysed towards their catalytic ability to produce the structurally related prodiginines. Besides the investigation of their substrate spectrum and enzyme kinetic data, a preparative scale biocatalysis approach for the production of prodiginine derivatives was established, comparing different condensing enzymes.

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Properties and applications of undecylprodigiosin and other bacterial prodigiosins

Cited by 123 publications

References 165 publications

Large-Scale Transposition Mutagenesis of Streptomyces coelicolor Identifies Hundreds of Genes Influencing Antibiotic Biosynthesis

Large-Scale Transposition Mutagenesis of Streptomyces coelicolor Identifies Hundreds of Genes Influencing Antibiotic Biosynthesis

The impact of concentration and administration time on the radiomodulating properties of undecylprodigiosin in vitro

Condensing Enzymes from Pseudoalteromonadaceae for Prodiginine Synthesis

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