A new strain of Serratia marcescens UCP1459 isolated from a semi-arid soil produced the natural red pigment prodigiosin, characterized by an uncommon pyrrolylpyrromethane skeleton. Prodigiosin is a ...promising drug due to its reported antifungal, immunosuppressive and anti-proliferative activities. The objective of this work was to indentify a suitable medium to simultaneously enhance S. marcescens growth and pigment production using renewable resources obtained from industrial wastes. S. marcescens produced the highest level of prodigiosin (49.5 g/L) at 48 h of cultivation using 6% "manipueira" (cassava wastewater) supplemented with mannitol (2%) at pH 7 and 28 °C. Carbohydrates in "manipueira" and mannitol play a role in the enhanced cell growth and prodigiosin production. The purified pigment extracted from the biomass was analyzed by mass spectrophotometry and showed the expected molecular weight of 324 Da corresponding to prodigiosin. In conclusion, we have successfully designed a new, economically feasible medium supporting enhanced S. marcescens growth and a high yield production of prodigiosin.
Efficacy of Serratia marcescens for pigment production and biological activity was investigated. Natural substrates like sweet potato, mahua flower extract (Madhuca latifolia L.), and sesam at ...different concentrations were taken. As a carbon source microorganism favored potato powder was followed by sesam and mannitol, and as nitrogen source casein hydrolysate was followed by yeast and malt extract. The effect of inorganic salts on pigment production was also studied. At final optimized composition of suitable carbon, nitrogen source, and trace materials and at suitable physiological conditions, prodigiosin production was 4.8 g L⁻¹. The isolated pigment showed antimicrobial activity against different pathogenic bacteria and fungi. Extracted pigment was characterized by spectroscopy, Fourier transform infrared (FTIR), and thin layer chromatography (TLC) which confirm production of biological compound prodigiosin. This study suggests that use of sweet potato powder and casein can be a potential alternative bioresource for commercial production of pigment prodigiosin.
•Prodigiosin was determined as eco-environmental algicide to Heterosigma akashiwo, a common HABs causing microalgae.•2, Prodigiosin induced ROS overproduction of microalgae which was the potential ...mechanism of lysing microalgal cells.•Overproduction of ROS destroyed cell integrity and changed antioxidant system levels and functional gene expression.
Harmful algal blooms (HABs) occur all over the world, producing severely negative effects on human life as well as on marine ecosystems. The algicidal compound, prodigiosin, secreted by algicidal bacteria Hahella sp. KA22 can lyse the harmful alga Heterosigma akashiwo. This study is aimed to investigate the algicidal mechanism of prodigiosin against H. akashiwo by detecting physiological and morphological responses of H. akashiwo to presence of prodigiosin. The results indicated that prodigiosin showed strong algicidal effects on H. akashiwo at the concentration of 3 μg/mL. Chlorophyll a and protein levels of the microalgae decreased significantly while malonaldehyde levels increased at this concentration. Contents of ascorbic acid and activities of superoxide dismutase and peroxidase increased fast with the quick decrease of the reactive oxygen species (ROS). For the 3 μg/mL prodigiosin treatment group, transcription of genes related to photosynthesis and respiration were significantly inhibited at 12 h while respiration related genes increased at 24 h. Collectively, the results indicated that prodigiosin could kill the microalgae by inducing ROS overproduction which could destroy the cell integrity and change the antioxidant system levels and functional gene expression. Our results demonstrated that prodigiosin is an effective algicide for the control of harmful algae.
•Bacteria isolated from waterfall was identified as Serratia nematodiphila.•The bacteria produced a red-pigment characterized as prodigiosin.•Addition of oil substrate increased the prodigiosin ...production in fermentation.•Palm oil gave the comparable improvement in prodigiosin production.•The prodigiosin showed photovoltaic properties, and could be used as photosensitizer.
Bacterial pigments are potential substitute of chemical photosensitizer for dye-sensitized solar cell (DSSC) due to its non-toxic property and cost-effective production from microbial fermentation. Serratia nematodiphila YO1 was isolated from waterfall in Malaysia and identified using 16S ribosomal RNA. Characterization of the red pigment produced by the bacteria has confirmed the pigment as prodigiosin. Prodigiosin was produced from the fermentation of the bacteria in the presence of different oil substrates. Palm oil exhibited the best performance of cell growth and equivalent prodigiosin yield compared to olive oil and peanut oil. Prodigiosin produced with palm oil supplementation was 93 mg/l compared to 7.8 mg/l produced without supplementation, which recorded 11.9 times improvement. Specific growth rate of the cells improved 1.4 times when palm oil was supplemented in the medium. The prodigiosin pigment produced showed comparable performance as a DSSC sensitizer by displaying an open circuit voltage of 336.1 mV and a maximum short circuit current of 0.098 mV/cm2. This study stands a novelty in proving that the production of prodigiosin is favorable in the presence of palm oil substrate with high saturated fat content, which has not been studied before. This is also among the first bacterial prodigiosin tested as photosensitizer for DSSC application.
Alphaproteobacterium strain MOLA1416, related to Mycoplana ramosa DSM 7292 and Chelativorans intermedius CC-MHSW-5 (93.6% 16S rRNA sequence identity) was isolated from the marine lichen, Lichina ...pygmaea and its chemical composition was characterized by a metabolomic network analysis using LC-MS/MS data. Twenty-five putative different compounds were revealed using a dereplication workflow based on MS/MS signatures available through GNPS (https://gnps.ucsd.edu/). In total, ten chemical families were highlighted including isocoumarins, macrolactones, erythrinan alkaloids, prodiginines, isoflavones, cyclohexane-diones, sterols, diketopiperazines, amino-acids and most likely glucocorticoids. Among those compounds, two known metabolites (13 and 26) were isolated and structurally identified and metabolite 26 showed a high cytotoxic activity against B16 melanoma cell lines with an IC50 0.6 ± 0.07 μg/mL.
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•Chemical investigation of a Rhizobiales strain associated with Lichina pygmaea.•Dereplication workflow based on MS/MS signatures and molecular networks were used.•25 putative known compounds were revealed.•2 metabolites were isolated and structurally identified.
•First complete genome of a prodigiosin-producing Janthinobacterium sp.•Potentially novel species based on phylogenomic analysis and genome indices.•Upregulated cold stress-responsive genes ...highlighted cold-adaptation in ERMR3:09.•Genome analysis revealed unique genes and gene cluster for prodigiosin biosynthesis.•Extracted pigment can find application as a natural antioxidant agent.
Janthinobacterium from cold niches has been studied broadly for bioactive violacein production. However, reports on the atypical red-pigmented Janthinobacterium strains are shallow. The bioactive red prodigiosin pigment has immense pharmacological significance, including antioxidant, antimicrobial and anticancer potential. Here, we report the first complete genome of a prodigiosin-producing Janthinobacterium sp. ERMR3:09 from Sikkim Himalaya in an attempt to elucidate its cold adaptation and prodigiosin biosynthesis. Nanopore sequencing and Flye assembly of the ERMR3:09 genome resulted in a single contig of 6,262,330 bp size and 62.26% GC content. Phylogenomic analysis and genome indices indicate that ERMR3:09 is a potentially novel species of the genus Janthinobacterium. The multicopy cold-responsive genes and gene upregulation under cold stress denoted its cold adaptation mechanisms. Genome analysis identified the unique genes, gene cluster and pathway for prodigiosin biosynthesis in ERMR3:09. Considering the notable antioxidant activity, it can be the next powerhouse of bioactive prodigiosin production.
The prodiginines are a group of specialized metabolites that share a 4-methoxypyrrolyldipyrromethene core structure. Streptorubin B is a structurally remarkable member of the prodiginine group ...produced by Streptomyces coelicolor A3(2) and other actinobacteria. It is biosynthesized from undecylprodigiosin by an oxidative carbocyclization catalyzed by the Rieske oxygenase-like enzyme RedG. Undecylprodigiosin derives from the RedH-catalyzed condensation of 2-undecylpyrrole and 4-methoxy-2, 2′-bipyrrole-5-carboxaldehyde (MBC). To probe the mechanism of the RedG-catalyzed reaction, we synthesized 2-(5-pentoxypentyl)-pyrrole, an analogue of 2-undecylpyrrole with an oxygen atom next to the site of C–C bond formation, and fed it, along with synthetic MBC, to Streptomyces albus expressing redH and redG. This resulted in the production of the 6′-oxa analogue of undecylprodigiosin. In addition, a small amount of a derivative of this analogue lacking the n-pentyl group was produced, consistent with a RedG catalytic mechanism involving hydrogen abstraction from the alkyl chain of undecylprodigiosin prior to pyrrole functionalization. To investigate the stereochemistry of the RedG-catalyzed oxidative carbocyclization, 7′-2H(7′R)-2-undecylpyrrole and 7′-2H(7′S)-2-undecylpyrrole were synthesized and fed separately, along with MBC, to S. albus expressing redH and redG. Analysis of the extent of deuterium incorporation into the streptorubin B produced in these experiments showed that the pro-R hydrogen atom is abstracted from C-7′ of undecylprodigiosin and that the reaction proceeds with inversion of configuration at C-7′. This contrasts sharply with oxidative heterocyclization reactions catalyzed by other nonheme iron-dependent oxygenase-like enzymes, such as isopenicillin N synthase and clavaminate synthase, which proceed with retention of configuration at the carbon center undergoing functionalization.
Background
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.
Methods and results
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).
Conclusions
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.
Prodiginines are a family of red-pigmented secondary metabolites with multiple biological activities. The biosynthesis of prodiginines is affected by various physiological and environmental factors. ...Thus, prodiginine biosynthesis regulation is highly complex and multifaceted. Although the regulatory mechanism for prodiginine biosynthesis has been extensively studied in
and
species, little is known about that in the marine betaproteobacterium
In this study, we report that stringent starvation protein A (SspA), an RNA polymerase-associated regulatory protein, is required for the biosynthesis of prodiginine in
sp. strain R3. The strain lacking
(Δ
) fails to produce prodiginine, which resulted from the downregulation of the prodiginine biosynthetic gene (
) cluster. The effect of SspA on prodiginine biosynthesis is independent of histone-like nucleoid structuring protein (H-NS) and RpoS (σ
). Further analysis demonstrates that the Δ
strain has a significant decrease in the transcription of the siderophore biosynthesis gene (
) cluster, leading to the inhibition of siderophore production and iron uptake. The Δ
strain regains the ability to synthesize prodiginine by cocultivation with siderophore producers or the addition of iron. Therefore, we conclude that SspA-regulated prodiginine biosynthesis is due to decreased siderophore levels and iron deficiency. We further show that the iron homeostasis master regulator Fur is also essential for
transcription and prodiginine biosynthesis. Overall, our results suggest that SspA indirectly regulates the biosynthesis of prodiginine, which is mediated by the siderophore-dependent iron uptake pathway.
The red-pigmented prodiginines are attracting increasing interest due to their broad biological activities. As with many secondary metabolites, the biosynthesis of prodiginines is regulated by both environmental and physiological factors. At present, studies on the regulation of prodiginine biosynthesis are mainly restricted to
and
species. This work focused on the regulatory mechanism of prodiginine biosynthesis in
sp. R3. We found that stringent starvation protein A (SspA) positively regulates prodiginine biosynthesis via affecting the siderophore-dependent iron uptake pathway. The connections among SspA, iron homeostasis, and prodiginine biosynthesis were investigated. These findings uncover a novel regulatory mechanism for prodigiosin biosynthesis.
Here, we report the first total synthesis of hybrubin A, a bipyrrole tetramic acid alkaloid representing a new carbon framework derived from convergent (truncated red cluster and exogenous hbn ...cluster) biosynthetic pathways. A highly convergent synthesis was developed, employing 4-methoxy-1,5-dihydro-2H-pyrrol-2-one (13) as a single starting material to provide hybrubin A in three steps from 13 and 20.8% overall yield. As no biological activity was prescribed to hybrubin A except for a lack of cytotoxicity, we further profiled this unique alkaloid across panels of discrete molecular targets. Interestingly, hybrubin A was found to be a ligand for a variety of GPCRs with a propensity for potent binding across therapeutically relevant adenosine receptors (A1, A2a, and A3) as well as a potent activity at a kinase, FLT3. This pattern of biological activity is distinct from other related prodigiosin natural and unnatural products and is even more intriguing in the absence of cytotoxicity.
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