Explore the vast range of titles available.

The negative environmental and social impacts of food waste accumulation can be mitigated by utilizing bio-refineries’ approach where food waste is revalorized into high-value products, such as prodigiosin (PG), using microbial bioprocesses. The diverse biological activities of PG position it as a promising compound, but its high production cost and promiscuous bioactivity hinder its wide application. Metal ions can modulate the electronic properties of organic molecules, leading to novel mechanisms of action and increased target potency, while metal complex formation can improve the stability, solubility and bioavailability of the parent compound. The objectives of this study were optimizing PG production through bacterial fermentation using food waste, allowing good quantities of the pure natural product for further synthesizing and evaluating copper(II) and zinc(II) complexes with it. Their antimicrobial and anticancer activities were assessed, and their binding affinity toward biologically important molecules, bovine serum albumin (BSA) and DNA was investigated by fluorescence emission spectroscopy and molecular docking. The yield of 83.1 mg/L of pure PG was obtained when processed meat waste at 18 g/L was utilized as the sole fermentation substrate. The obtained complexes CuPG and ZnPG showed high binding affinity towards target site III of BSA, and molecular docking simulations highlighted the affinity of the compounds for DNA minor grooves.

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.

Tripyrrole molecules have received renewed attention due to reports of numerous biological activities, including antifungal, antibacterial, antiprotozoal, antimalarial, immunosuppressive, and anticancer activities. In a screen of bacterial strains with known toxicities to termites, a red pigment-producing strain, HDZK-BYSB107, was isolated from Chamaecyparis lawsoniana, which grows in Oregon, USA. Strain HDZK-BYSB107 was identified as Serratia marcescens subsp. lawsoniana. The red pigment was identified as prodigiosin using ultraviolet absorption, LC-MS, and 1H-NMR spectroscopy. The bacterial prodigiosin had an inhibitory effect on both Gram-negative and Gram-positive bacteria. The main objective of this study was to explore the anticancer activities and mechanism of strain HDZK-BYSB107 prodigiosin by using human choriocarcinoma (JEG3) and prostate cancer cell lines (PC3) in vitro and JEG3 and PC3 tumor-bearing nude mice in vivo. In vitro anticancer activities showed that the bacterial prodigiosin induced apoptosis in JEG3 cells. In vivo anticancer activities indicated that the prodigiosin significantly inhibited the growth of JEG3 and PC3 cells, and the inhibitory activity was dose and time dependent. The anticancer efficacy of the bacterial prodigiosin on JEG3 and PC3 cells, JEG3 and PC3 tumor exhibited a correlation with the down regulation of the inhibitor of IAP family, including XIAP, cIAP-1 and cIAP-2, and the activation of caspase-9 and caspase-3 accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. The expressions of P53 and Bax/Bcl-2 in JEG3 and PC3 cells were significantly higher than in untreated groups. Our results indicated that the bacterial prodigiosin extracted from C. lawsoniana is a promising molecule due to its potential for therapeutic applications.

The red color pigment prodigiosin is a potent antioxidant produced by different strains of Serratia marcescens and other bacteria. The bio pigment demonstrates many hopeful impending bioactivities. Prodigiosin is an active proapoptotic agent against various cancer cell lines. In the present study, pigment produced from soil isolate Serratia marcescens VITSD2 was characterized and identified using UV, FTIR, GC‐MS and NMR analysis (1H NMR and 13C NMR). The antiproliferative activity of prodigiosin pigment from Serratia marcescens VITSD2 was evaluated on cancer cell lines. The active sites and binding patterns of molecular marker survivin was analyzed on docking against prodigiosin.A strong antioxidant potential was noticed at 5 mg/mL concentration with 70 ± 0.08% scavenging activity (2,2‐diphenyl‐1‐picrylhydrazyl)‐DPPH. The dose dependent inhibition of HepG2 cell proliferation was observed maximum with 67 ± 0.08% cytotoxic activity at 50 µg/mL. When compared to other cell lines, A549, HL 60 and MCF‐7, prodigiosin had a strong inhibitory activity on HepG2 cells. The Rf value of single band obtained in chromatography showed a value of 0.45. Maximum absorbance was observed at 535 nm. The pigment revealed the characteristic functional properties of the prodigiosin. On docking, the lowest binding energy exhibited was found to be ‐5.15 kcal/mol. The RMSD analysis indicated that the backbone structure converges at 18 ns before it attains stability. Pigment production from Serratia marcescens VIT SD2 offer a renewable and sustainable alternative to synthetic pigments, reducing dependence on nonrenewable resources. The study outcomes specified that the bio pigment prodigiosin extracted from Serratia marcescens VIT SD2 is a promising drug candidate for therapeutics. 1. Prodigiosin pigment from Serratia marcescens VITSD2 was structurally characterized using UV, FTIR, GC‐MS, and NMR techniques. 2. It showed strong cytotoxic activity on HepG2 cells (67 ± 0.08% at 50 µg/mL), outperforming effects on A549, HL60, and MCF‐7 lines. 3. Molecular docking with survivin revealed stable binding ( − 5.15 kcal/mol), supporting its proapoptotic role. 4. The pigment exhibited 70 ± 0.08% antioxidant activity at 5 mg/mL, highlighting its therapeutic potential as a sustainable natural drug.

Marine chitins (MC) have been utilized for the production of vast array of bioactive products, including chitooligomers, chitinase, chitosanase, antioxidants, anti-NO, and antidiabetic compounds. The aim of this study is the bioprocessing of MC into a potent anticancer compound, prodigiosin (PG), via microbial fermentation. This bioactive compound was produced by Serratia marcescens TKU011 with the highest yield of 4.62 mg/mL at the optimal conditions of liquid medium with initial pH of 5.65–6.15 containing 1% α-chitin, 0.6% casein, 0.05% K2HPO4, and 0.1% CaSO4. Fermentation was kept at 25 °C for 2 d. Notably, α-chitin was newly investigated as the major potential material for PG production via fermentation; the salt CaSO4 was also found to play the key role in the enhancement of PG yield of Serratia marcescens fermentation for the first time. PG was qualified and identified based on specific UV, MALDI-TOF MS analysis. In the biological activity tests, purified PG demonstrated potent anticancer activities against A549, Hep G2, MCF-7, and WiDr with the IC50 values of 0.06, 0.04, 0.04, and 0.2 µg/mL, respectively. Mytomycin C, a commercial anti-cancer compound was also tested for comparison purpose, showing weaker activity with the IC50 values of 0.11, 0.1, 0.14, and 0.15 µg/mL, respectively. As such, purified PG displayed higher 2.75-fold, 1.67-fold, and 3.25-fold efficacy than Mytomycin C against MCF-7, A549, and Hep G2, respectively. The results suggest that marine chitins are valuable sources for production of prodigiosin, a potential candidate for cancer drugs.

Key Points Prodiginines are a family of tripyrrole, red pigments which are attracting increasing interest because of their immunosuppressive and anticancer activities. Currently prodigiosin and a synthetic derivative are in pre-clinical and phase I/II clinical trails, respectively, as treatments for different types of cancer. Prodiginines are produced by Serratia spp., actinomycetes (for example, Streptomyces coelicolor A3(2)) and various marine bacteria, including Hahella chejuensis KCTC 2396 and Pseudoalteromonas denitrificans . Examples of prodiginines include prodigiosin, undecylprodigiosin and cyclic derivatives such as butyl-meta-cycloheptylprodiginine produced by Streptomyces coelicolor . As with many secondary metabolites, the true physiological role of prodiginines in the producer organisms is still debated. Suggested roles have included antibacterial, antifungal or trypanolytic agents, aiding surface adherence, enhancing bacterial dispersal and functioning as a metabolic sink. Biosynthesis of prodiginines proceeds by a bifurcated pathway culminating in the PigC/RedH catalysed condensation of the terminal products of the two pathways, a monopyrrole (2-methyl-3-n-amyl-pyrrole ( Serratia ) or 2-undecylpyrrole ( Streptomyces ) and 4-methoxy-2,2′-bipyrrole-5-carbaldehyde (MBC) to form prodigiosin. A common pathway to the biosynthesis of MBC exists, requiring PigA, PigF, PigG, PigH, PigI, PigJ, PigL, PigM and PigN and their respective S. coelicolor A3(2) homologues. The biosynthesis of the monopyrrroles proceeds by completely different pathways, catalysed by different sets of enzymes. The first steps in the biosynthesis of MBC have been shown biochemically to involve the incorporation of L -proline to form the pyrrole ring through a pyrrolyl-2-carboxyl- S -PCP intermediate catalysed by RedM, RedO and RedW. This mechanism for the incorporation of proline into a pyrrole is common to many pyrrole-containing compounds, including undecylprodigiosin, prodigiosin, pyoluteorin, coumermycin A1, novobiocin and chlorobiocin. The production of prodiginines is exquisitely sensitive to numerous environmental and physiological cues, including temperature and carbon source. For example, inorganic phosphate limitation, by the Pho regulon, activates prodiginine synthesis in both Serratia 39006 and S. coelicolor A3(2). Cell–cell communication by extracellular signalling (quorum sensing) regulates prodiginine biosynthesis by γ-butyrolactones in S. coelicolor A3(2) and N -AHLs, and furanosyl borate diesters or related molecules in Serratia spp. Multiple membrane-associated signalling proteins, including two-component systems, also regulate the production of prodiginines in Serratia 39006 and S. coelicolor A3(2), in response to external signals. The small, highly phosphorylated nucleotide ppGpp interacts with RNA polymerase to control undecylprodigiosin production in S. coelicolor A3(2) in response to nitrogen starvation. In addition, transcription of the undecylprodigiosin biosynthetic cluster requires two linked pathway-specific activators, RedD and RedZ. In S. marcescens the modular nature of the prodigiosin biosynthetic loci and the quorum-sensing genes enabled the horizontal transfer of biosynthetic and regulatory loci. This resulted in certain strains immediately acquiring the ability to produce and/or regulate the biosynthesis of this secondary metabolite. The horizontally mobile nature of prodigiosin production, coupled with the understanding of the substrate flexibility of some of the biosynthetic enzymes, highlights the adaptive plasticity of bacterial secondary metabolism and might enable the evolution and engineering of strains capable of producing a range of prodiginine derivatives with biotechnological uses. Prodiginines are a family of secondary metabolites produced by Gram-positive and Gram-negative bacteria that have anticancer and immunosuppressive activities. The biosynthesis of these tripyrrole red pigments is reviewed, together with a discussion of the exquisite regulation of the production of these molecules, and why bacteria might benefit from producing such complex products. The red-pigmented prodiginines are bioactive secondary metabolites produced by both Gram-negative and Gram-positive bacteria. Recently, these tripyrrole molecules have received renewed attention owing to reported immunosuppressive and anticancer properties. The enzymes involved in the biosynthetic pathways for the production of two of these molecules, prodigiosin and undecylprodigiosin, are now known. However, the biochemistry of some of the reactions is still poorly understood. The physiology and regulation of prodiginine production in Serratia and Streptomyces are now well understood, although the biological role of these pigments in the producer organisms remains unclear. However, research into the biology of pigment production will stimulate interest in the bioengineering of strains to synthesize useful prodiginine derivatives.

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, in vivo, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from Serratia marcescens subsp. lawsoniana was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.

Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are currently under preclinical and clinical trials. The molecular target(s) of these agents, however, is an open question. Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2 protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the development of more specific inhibitors of anti-apoptotic BCL-2 proteins.

Parasitic infections are a major source of human suffering, mortality, and economic loss, but drug development for these diseases has been stymied by the significant expense involved in bringing a drug though clinical trials and to market. Identification of single compounds active against multiple parasitic pathogens could improve the economic incentives for drug development as well as simplifying treatment regimens. We recently performed a screen of repurposed compounds against the protozoan parasite Entamoeba histolytica, causative agent of amebic dysentery, and identified four compounds (anisomycin, prodigiosin, obatoclax and nithiamide) with low micromolar potency and drug-like properties. Here, we extend our investigation of these drugs. We assayed the speed of killing of E. histolytica trophozoites and found that all four have more rapid action than the current drug of choice, metronidazole. We further established a multi-institute collaboration to determine whether these compounds may have efficacy against other parasites and opportunistic pathogens. We found that anisomycin, prodigiosin and obatoclax all have broad-spectrum antiparasitic activity in vitro, including activity against schistosomes, T. brucei, and apicomplexan parasites. In several cases, the drugs were found to have significant improvements over existing drugs. For instance, both obatoclax and prodigiosin were more efficacious at inhibiting the juvenile form of Schistosoma than the current standard of care, praziquantel. Additionally, low micromolar potencies were observed against pathogenic free-living amebae (Naegleria fowleri, Balamuthia mandrillaris and Acanthamoeba castellanii), which cause CNS infection and for which there are currently no reliable treatments. These results, combined with the previous human use of three of these drugs (obatoclax, anisomycin and nithiamide), support the idea that these compounds could serve as the basis for the development of broad-spectrum anti-parasitic drugs.

The growing demand to fulfill the needs of present-day medicine in terms of novel effective molecules has lead to reexamining some of the old and known bacterial secondary metabolites. Bacterial prodigiosins (prodiginines) have a long history of being re markable multipurpose compounds, best examined for their anticancer and antimalarial activities. Production of prodigiosin in the most common producer strain Serratia marcescens has been described in great detail. However, few reports have discussed the ecophysiological roles of these molecules in the producing strains, as well as their antibiotic and UV-protective properties. This review describes recent advances in the production process, biosynthesis, properties, and applications of bacterial prodigiosins. Special emphasis is put on undecylprodigiosin which has generally been a less studied member of the prodigiosin family. In addition, it has been suggested that proteins involved in undecylprodigiosin synthesis, RedG and RedH, could be a useful addition to the biocatalytic toolbox being able to mediate regio- and stereoselective oxidative cyclization. Judging by the number of recent references (216 for the 2007–2013 period), it has become clear that undecylprodigiosin and other bacterial prodigiosins still hold surprises in terms of valuable properties and applicative potential to medical and other industrial fields and that they still deserve continuing research curiosity.