Jasmina Nikodinovic | University College Dublin (original) (raw)

Papers by Jasmina Nikodinovic

Journal of Materials Chemistry B, 2014

ABSTRACT Bacterial pigment undecylprodigiosin (UP) was produced using Streptomyces sp. JS520 and ... more ABSTRACT Bacterial pigment undecylprodigiosin (UP) was produced using Streptomyces sp. JS520 and conjugated to monodisperse gold nanoparticles (UP-Au). Both UP and UP-Au showed cytocidal activity towards melanoma (A375), lung carcinoma (A549), breast cancer (MCF-7) and colon cancer (HCT-116) cell lines, inducing apoptosis with IC50 values ranging from 0.4 to 4 μg/ml. Unconjugated UP had tendency to lose its activity over time and to change biophysical characteristics over pH. The loss of the pigment potency was overcome by conjugation with gold nanoparticles. UP-Au exhibited high stability over pH 3.8 to 7.4 and its activity remained unaffected in time. Nano-packing changed the mechanism of UP toxicity by converting the intracellular signals from mitochondrial dependent to mitochondrial independent apoptotic process. Availability of nonpyrogenic UP in high amounts, together with specific anticancer activity and improved stability in the complex with gold nanoparticles present a novel platform for further development of UP-Au complexes as an anticancer drug suitable for clinical applications.

Industrial Crops and Products, 2015

Antifungal effect of individual thyme (Thymus vulgaris L.) and cinnamon (Cinnamomum cassia L.) es... more Antifungal effect of individual thyme (Thymus vulgaris L.) and cinnamon (Cinnamomum cassia L.) essential oils (EOs) and mixture of thereof on Aspergillus flavus spores was investigated. In order to optimize the process variables (time of action, concentration of individual or mixture EOs and their mass ratio) for the antifungal effect of EO mixture, two models were developed: the response surface methodology (RSM) and artificial neural network (ANN) combined with genetic algorithm (GA). In RSM model, three factors were involved in Box-Behnken design that was applied for the experiment. Based on the mean relative percent deviation (MRPD), both models provided a good quality prediction for the antifungal effect in terms of all three process variables. RSM and ANN-GA techniques predicted the 0.5% as an optimum percentage concentration of EO mixture in EOs mass ratio T. vulgaris:C. cassia 1:1, ensuring the highest antifungal effect of 95.8% and 96.4% after 65 min. Both models were found useful for the optimization of the antifungal effect in vitro. ANN-GA was found more accurate in comparison to RSM due to its lower value of MRPD. Therefore, ANN-GA can be generally used for optimization and prediction of antimicrobial effects of EOs and their mixtures.

Chemico-Biological Interactions, 2015

12 13 1 5 a r t i c l e i n f o 16 Article history: 17 Available online xxxx 18 Keywords: 19 4-Ph... more 12 13 1 5 a r t i c l e i n f o 16 Article history: 17 Available online xxxx 18 Keywords: 19 4-Phenyl hydroxycoumarins 20 Cytotoxicity 21 Molecular docking 22 Teratogenic potential 23 Protein kinase inhibitors 24 2 5 a b s t r a c t 26 A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic 27 coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is present-28 ed. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-29 dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's 30 number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at 31 the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking 32 studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-de-33 pendent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic poten-34 tial was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins 35 were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In 36 order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of 37 selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's ''rule of five''. All selected 4-phe-38 nyl hydroxycoumarins proved to have satisfying pharmacokinetic profile.

Genetika, 2013

ABSTRACT Identification and characterization of novel genes belonging to microbial aromatic biode... more ABSTRACT Identification and characterization of novel genes belonging to microbial aromatic biodegradation pathway is of great importance as they have been proven versatile biocatalysts. In this study, the selection of 19 environmental bacterial isolates capable to degrade a wide range of aromatic compounds has been screened for the presence of five genes from the lower and the upper aromatic biodegradation pathway using PCR methodology. In the case of 4-oxalocrotonate tautomerase and toluene dioxygenases, although present in the most of environmental isolates, very limited diversity of the genes has been encountered. Highly conserved sequences of these genes in environmental samples revealed high homology with gene sequences of the characterised corresponding genes from Pseudomonas putida species. The screen using degenerate primers based on known catechol-and naphthalene dioxygenases sequences resulted in a limited number of amplified fragments. Only two catechol 2,3-dioxygenase from two Bacillus isolates were amplified and showed no significant similarities with dioxygenases from characterized organisms, but 80-90% identities with partial catechol 2,3-dioxygenase sequences from uncultured organisms. Potentially three novel catechol 1,2-dioxygenases were identified from Bacillus sp. TN102, Gordonia sp. TN103 and Rhodococcus sp. TN112. Highly homologous tautomerase and toluene dioxygenases amongst environmental samples isolated from the contaminated environment suggested horizontal gene transfer while limited success in PCR detection of the other three genes indicates that these isolates may still be a source of novel genes.

Biotechnology Letters, 2015

Recent developments in biocatalysis, where implementation beyond the laboratory has been demonstr... more Recent developments in biocatalysis, where implementation beyond the laboratory has been demonstrated, are explored: the use of transglutaminases to modify foods, reduce allergenicity and produce advanced materials, lipases for biodiesel production, and transaminases for biochemical production. The availability and application of enzymes at pilot and larger scale opens up possibilities for further improvements of biocatalyst-based processes and the development of new processes. Enzyme production, stability, activity, re-use, and product retrieval are common challenges for biocatalytic processes. We explore recent advances in biocatalysis within the process chain, such as protein engineering, enzyme expression, and biocatalyst immobilization, in the context of these challenges.

Journal of Hazardous Materials, 2012

Gram-positive bacteria from river sediments affected by the proximity of a petrochemical industri... more Gram-positive bacteria from river sediments affected by the proximity of a petrochemical industrial site were isolated and characterized with respect to their ability to degrade a wide range of aromatic compounds. In this study we identified metabolically diverse Gram-positive bacteria capable of growth on wide range aromatic compounds in the presence of heavy metals and with the ability to accumulate biopolymers. Thirty-four isolates that were able to use 9 or more common aromatic pollutants, such as benzene, biphenyl, naphthalene etc. as a sole source of carbon and energy included members of Bacillus, Arthrobacter, Rhodococcus, Gordonia, Streptomyces, and Staphylococcus genus. Rhodococcus sp. TN105, Gordonia sp. TN103 and Arthrobacter sp. TN221 were identified as novel strains. Nine isolates were able to grow in the presence of one or more metals (mercury, cadmium, nickel) at high concentration (100 mM). Seven isolates could degrade 15 different aromatic compounds and could grow in the presence of one or more heavy metals. Two of these isolates were resistant to multiple antibiotics including erythromycin and nalidixic acid. One third of isolates could accumulate at least one biopolymer. Twelve isolates (mainly Bacillus sp. and Arthrobacter sp.) accumulated polyphosphate, 3 Bacillus sp. accumulated polyhydroxybutyrate, while 4 isolates could accumulate exopolysaccharides.

Journal of Applied Microbiology, 2012

Aims: The aim of this study was to convert numerous polyaromatic and monoaromatic hydrocarbons in... more Aims: The aim of this study was to convert numerous polyaromatic and monoaromatic hydrocarbons into biodegradable polymer medium-chain-length polyhydroxyalkanoate (mcl-PHA). Methods and Results: Using naphthalene enrichment cultivation method, we have isolated seven bacterial strains from the river sediment exposed to petrochemical industry effluents. In addition to naphthalene, all seven strains could utilize between 12 and 17 different aromatic substrates, including toluene, benzene and biphenyl. Only one isolate that was identified as Pseudomonas sp. TN301 could accumulate mcl-PHA from naphthalene to 23% of cell dry weight. Owing to poor solubility, a method of supplying highly hydrophobic polyaromatic hydrocarbons to a culture medium was developed. The best biomass and mcl-PHA yields were achieved with the addition of synthetic surfactant Tween 80 (0·5 g l À1 ). We have shown that Pseudomonas sp. TN301 can accumulate mcl-PHA from a wide range of polyaromatic and monoaromatic hydrocarbons, and mixtures thereof, while it could also accumulate polyphosphates and was tolerant to the presence of heavy metal (100 mmol l À1 cadmium and 20 mmol l À1 nickel). Conclusions: A new Pseudomonas strain was isolated and identified with the ability to accumulate mcl-PHA from a variety of aromatic hydrocarbons. Significance and Impact of the Study: This study is the first report on the ability of a bacterial strain to convert a range of polyaromatic hydrocarbon compounds to the biodegradable polymer (mcl-PHA). Mcl-PHA is gaining importance as a promising biodegradable thermoelastomer, and therefore, isolation of new producing strains is highly significant. Furthermore, this strain has the ability to utilize a range of hydrocarbons, which often occur as mixtures and could potentially be employed in the recently described efforts to convert waste materials to PHA.

Biotechnology Letters, 2013

1-(3,4-Dihydroxyphenyl) ethanol was produced biocatalytically for the first time using mushroom t... more 1-(3,4-Dihydroxyphenyl) ethanol was produced biocatalytically for the first time using mushroom tyrosinase. 4-Ethylphenol at 1 mM was consumed over 12 min giving 0.23 mM 4-ethylcatechol and 0.36 mM (R/S)-1-(3,4-dihydroxyphenyl) ethanol (ee 0.5 %). Mushroom tyrosinase consumed 4-ethylphenol at 6.7 μmol min(-1) mg protein(-1) while the rates of formation of 4-ethylcatechol and 1-(3,4-dihydroxyphenyl) ethanol were 1.1 and 1.9 μmol min(-1) mg protein(-1). Addition of the ascorbic acid, as a reducing agent to biotransformation reactions, increased 4-ethylcatechol formation by 340 %. However, accumulation of 1-(3,4-dihydroxyphenyl) ethanol was not observed in the presence of ascorbic acid. While the 1-(3,4-dihydroxyphenyl) ethanol was racemic, it is the first chiral product produced by tyrosinase starting from a non-chiral substrate.

Biotechnology and Bioengineering, 2011

The improvement and modeling of a process for the supply of the volatile aromatic hydrocarbon, st... more The improvement and modeling of a process for the supply of the volatile aromatic hydrocarbon, styrene, to a fermentor for increased biomass production of the medium chain length polyhydroxyalkanoate (mcl-PHA) accumulating bacterium Pseudomonas putida CA-3 was investigated. Fed-batch experiments were undertaken using different methods to provide the styrene. Initial experiments where styrene was supplied as a liquid to the bioreactor had detrimental effects on cell growth and inhibited PHA polymer accumulation. By changing the feed of gaseous styrene to liquid styrene through the air sparger a 5.4-fold increase in cell dry-weight was achieved (total of 10.56 g L À1 ) which corresponds to a fourfold improvement in PHA production (3.36 g L À1 ) compared to previous studies performed in our laboratory (0.82 g L À1 ). In addition this final improved feeding strategy reduced the release of styrene from the fermentor 50-fold compared to initial experiments (0.12 mL total styrene released per 48 h run). An unstructured kinetic model was developed to describe cell growth along with substrate and oxygen utilization. The formation of dispersed gas (air) and liquid (styrene) phases in the medium and the transfer of styrene between the aqueous and dispersed liquid droplet phases was also modeled. The model provided a detailed description of these phase transitions and helped explain how the feeding strategy led to improved process performance in terms of final biomass levels. It also highlighted the key factors to be considered during further process improvement.

Biotechnology and Bioengineering, 2013

The tyrosinase gene from Ralstonia solanacearum (GenBank NP518458) was subjected to random mutage... more The tyrosinase gene from Ralstonia solanacearum (GenBank NP518458) was subjected to random mutagenesis resulting in tyrosinase variants (RVC10 and RV145) with up to 3.2-fold improvement in k(cat), 5.2-fold lower K(m) and 16-fold improvement in catalytic efficiency for D-tyrosine. Based on RVC10 and RV145 mutated sequences, single mutation variants were generated with all variants showing increased k(cat) for D-tyrosine compared to the wild type (WT). All single mutation variants based on RV145 had a higher k(cat) and K(m) value compared to the RV145 and thus the combination of four mutations in RV145 was antagonistic for turnover, but synergistic for affinity of the enzyme for D-tyrosine. Single mutation variant 145_V153A exhibited the highest (6.9-fold) improvement in k(cat) and a 2.4-fold increase in K(m) compared to the WT. Two single mutation variants, C10_N322S and C10_T183I reduced the K(m) up to 2.6-fold for D-tyrosine but one variant 145_V153A increased the K(m) 2.4-fold compared to the WT. Homology based modeling of R. solanacearum tyrosinase showed that mutation V153A disrupts the van der Waals interactions with an α-helix providing one of the conserved histidine residues of the active site. The k(cat) and K(m) values for L-tyrosine decreased for RV145 and RVC10 compared to the WT. RV145 exhibited a 2.1-fold high catalytic efficiency compared to the WT which is a 7.6-fold lower improvement compared to D-tyrosine. RV145 exhibited a threefold higher monophenolase:diphenolase activity ratio for D-tyrosine:D-DOPA and a 1.4-fold higher L-tyrosine:L-DOPA activity ratio compared to the WT.

Archives of Biological Sciences, 2011

Two novel Bacillus sp. were isolated from a soil sample from a bank of the Tamiš river in close p... more Two novel Bacillus sp. were isolated from a soil sample from a bank of the Tamiš river in close proximity to a petrochemical facility. They were capable of utilizing a broad range of aromatic compounds as a sole source of carbon and energy (including phenol, benzene, toluene, biphenyl, naphthalene). The isolates were designated as Bacillus sp. TN41 and TN42, based on their 16S rDNA sequence. Their catabolic potential was compared to two Bacillus sp. strains (PS1 and PS11) isolated from the rhizosphere of the endemorelict plant Ramonda serbica. Specific activities of phenol hydroxylase, catechol 1,2-dioxygenase and catechol 2,3-dioxygenase were analyzed from crude cell extracts of the isolates, as well as the temperature and pH effects on enzyme activity. Although all four isolates had the ability to degrade a similar range of aromatic compounds, the specific activities of the enzymes indicative of aromatic compound catabolism of TN isolates were 2 to 90-fold lower compared to the PS isolates. Phenol hydroxylase and catechol dioxygenases exhibited broad temperature (10°C-80°C) and pH (4-9) activity ranges in all four Bacillus isolates. While phenol inhibited both phenol hydroxylase and catechol dioxygenases in the TN strains, it was an inducer for phenol hydroxylase in the PS strains.

Archives of Biological Sciences, 2013

The bacterial diversity of the surface and deep sediment of the Copper Mining and Smelting Comple... more The bacterial diversity of the surface and deep sediment of the Copper Mining and Smelting Complex Bor, Serbia, was investigated using culture-dependent and culture-independent approaches. Sequencing analysis of 16S rDNA libraries revealed greater bacterial diversity in the surface sediment of the mining complex (MS) in comparison to deeper mine sediment (MU). While in the MS sample members of seven different phylogenetic groups were detected, in the MU sample library representatives of only three different groups were detected. The use of a culture-dependent approach revealed the presence of only three bacterial groups in both samples: Actinobacteria, Firmicutes and Proteobacteria, while six isolates exhibiting the highest metal tolerance were members of Arthrobacter and Staphylococcus genera. The most promising isolate, MSI08, was able to grow in the presence of high concentrations of Cd 2+ (535 µM), Ni 2+ (17 mM) and Cr 6+ (38.5 mM) and as such this indigenous strain has potential in the bioremediation of the contaminated surrounds of the city of Bor.

Applied Microbiology and Biotechnology, 2014

The growing demand to fulfill the needs of presentday medicine in terms of novel effective molecu... more The growing demand to fulfill the needs of presentday 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 2 0 0 7 -2 0 1 3 p e r i o d ) , i t h a s b e c o m e c l e a r t h a t 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.

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Applied Microbiology and Biotechnology, 2013

Nine different sulfur-containing compounds were biotransformed to the corresponding sulfoxides by... more Nine different sulfur-containing compounds were biotransformed to the corresponding sulfoxides by Escherichia coli Bl21(DE3) cells expressing styrene monooxygenase (SMO) from Pseudomonas putida CA-3. Thioanisole was consumed at 83.3 μmoles min(-1) g cell dry weight(-1) resulting mainly in the formation of R-thioanisole sulfoxide with an enantiomeric excess (ee) value of 45 %. The rate of 2-methyl-, 2-chloro- and 2-bromo-thioanisole consumption was 2-fold lower than that of thioanisole. Surprisingly, the 2-methylthioanisole sulfoxide product had the opposite (S) configuration to that of the other 2-substituted thioanisole derivatives and had a higher ee value (84 %). The rate of oxidation of 4-substituted thioanisoles was higher than the corresponding 2-substituted substrates but the ee values of the products were consistently lower (10-23 %). The rate of benzo[b]thiophene and 2-methylbenzo[b]thiophene sulfoxidation was approximately 10-fold lower than that of thioanisole. The ee value of the benzo[b]thiophene sulfoxide could not be determined as the product racemized rapidly. E. coli cells expressing an engineered SMO (SMOeng R3-11) oxidised 2-substituted thioanisoles between 1.8- and 2.8-fold faster compared to cells expressing the wild-type enzyme. SMOeng R3-11 oxidised benzo[b]thiophene and 2-methylbenzo[b]thiophene 10.1 and 5.6 times faster that the wild-type enzyme. The stereospecificity of the reaction catalysed by SMOeng was unchanged from that of the wild type. Using the X-ray crystal structure of the P. putida S12 SMO, it was evident that the entrance of substrates into the SMO active site is limited by the binding pocket bottleneck formed by the side chains of Val-211 and Asn-46 carboxyamide group.

Applied Microbiology and Biotechnology, 2012

Sodium terephthalate (TA) produced from a PET pyrolysis product and waste glycerol (WG) from biod... more Sodium terephthalate (TA) produced from a PET pyrolysis product and waste glycerol (WG) from biodiesel manufacture were supplied to Pseudomonas putida GO16 in a fed-batch bioreactor. Six feeding strategies were employed by altering the sequence of TA and WG feeding. P. putida GO16 reached 8.70 g/l cell dry weight (CDW) and 2.61 g/l PHA in 48 h when grown on TA alone. When TA and WG were supplied in combination, biomass productivity (g/l/h) was increased between 1.3-and 1.7-fold and PHA productivity (g/l/h) was increased 1.8-to 2.2-fold compared to TA supplied alone. The monomer composition of the PHA accumulated from TA or WG was predominantly composed of 3-hydroxydecanoic acid. PHA monomers 3hydroxytetradeeanoic acid and 3-hydroxytetradecenoic acid were not present in PHA accumulated from TA alone but were present when WG was supplied to the fermentation. When WG was either the sole carbon source or the predominant carbon source supplied to the fermentation the molecular weight of PHA accumulated was lower compared to PHA accumulated when TA was supplied as the sole substrate. Despite similarities in data for the properties of the polymers, PHAs produced with WG present in the PHA accumulation phase were tacky while PHA produced where TA was the sole carbon substrate in the polymer accumulation phase exhibited little or no tackiness at room temperature. The co-feeding of WG to fermentations allows for increased utilisation of TA. The order of feeding of WG and TA has an effect on TA utilisation and polymer properties.

Journal of Applied Microbiology 08/2013; DOI:10.1111/jam.12326

ABSTRACT The aim of this study was to improve production of pentaene 32,33-didehydroroflamycoin (... more ABSTRACT The aim of this study was to improve production of pentaene 32,33-didehydroroflamycoin (DDHR) in Streptomyces durmitorensis MS405 strain in order to obtain quantities sufficient for in depth analysis of antimicrobial properties.
Through classical medium optimization conditions for stable growth, DDHR production within 7 days of incubation was established. Yields of 215 mg l(-1) were achieved in shake flask experiments in complex medium with mannitol as the primary carbon source. DDHR had poor antibacterial activity with minimal inhibitory concentrations (MIC) of 400 μg ml(-1) for Staphylococcus aureus and Bacillus subtilis, while MIC of 70 μg ml(-1) was determined for Candida albicans. Using flow cytometry and fluorescent microscopy it was demonstrated that DDHR induced membrane damage in C. albicans followed by cell death. Combination studies with known antifungal nystatin showed that DDHR is a promising agent for the development of novel antimycotic treatments potentially less toxic for human cells.
Pentaene didehydroroflamycoin has no antibacterial activity but can be further developed for the application in antifungal therapy.
This study is the first report on the stable and production in high yields of a novel pentaene family that acts on Candida cell membranes and can be used in combination with known antifungals. Polyenes are still antifungal antibiotics of choice and therefore isolation and production of new lead structures is highly significant.