TY  - JOUR
AU  - Schneider, Olha
AU  - Ilić-Tomić, Tatjana
AU  - Rueckert, Christian
AU  - Kalinowski, Joern
AU  - Gencić, Marija S.
AU  - Zivković, Milena Z.
AU  - Stanković, Nada
AU  - Radulović, Niko S.
AU  - Vasiljević, Branka
AU  - Nikodinović-Runić, Jasmina
AU  - Zotchev, Sergey B.
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1107
AB  - Streptomyces sp. NP10 was previously shown to synthesize large amounts of free fatty acids (FFAs). In this work, we report the first insights into the biosynthesis of these fatty acids (FAs) gained after genome sequencing and identification of the genes involved. Analysis of the Streptomyces sp. NP10 draft genome revealed that it is closely related to several strains of Streptomyces griseus. Comparative analyses of secondary metabolite biosynthetic gene clusters, as well as those presumably involved in FA biosynthesis, allowed identification of an unusual cluster C12-2, which could be identified in only one other S. griseus-related streptomycete. To prove the involvement of identified cluster in FFA biosynthesis, one of its three ketosynthase genes was insertionally inactivated to generate mutant strain mNP10. Accumulation of FFAs in mNP10 was almost completely abolished, reaching less than 0.01% compared to the wild-type strain. Cloning and transfer of the C12-2 cluster to the mNP10 mutant partially restored FFA production, albeit to a low level. The discovery of this rare FFA biosynthesis cluster opens possibilities for detailed characterization of the roles of individual genes and their products in the biosynthesis of FFAs in NP10.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Microbiology
T1  - Genomics-Based Insights Into the Biosynthesis and Unusually High Accumulation of Free Fatty Acids by Streptomyces sp NP10
VL  - 9
DO  - 10.3389/fmicb.2018.01302
ER  - 

@article{
author = "Schneider, Olha and Ilić-Tomić, Tatjana and Rueckert, Christian and Kalinowski, Joern and Gencić, Marija S. and Zivković, Milena Z. and Stanković, Nada and Radulović, Niko S. and Vasiljević, Branka and Nikodinović-Runić, Jasmina and Zotchev, Sergey B.",
year = "2018",
abstract = "Streptomyces sp. NP10 was previously shown to synthesize large amounts of free fatty acids (FFAs). In this work, we report the first insights into the biosynthesis of these fatty acids (FAs) gained after genome sequencing and identification of the genes involved. Analysis of the Streptomyces sp. NP10 draft genome revealed that it is closely related to several strains of Streptomyces griseus. Comparative analyses of secondary metabolite biosynthetic gene clusters, as well as those presumably involved in FA biosynthesis, allowed identification of an unusual cluster C12-2, which could be identified in only one other S. griseus-related streptomycete. To prove the involvement of identified cluster in FFA biosynthesis, one of its three ketosynthase genes was insertionally inactivated to generate mutant strain mNP10. Accumulation of FFAs in mNP10 was almost completely abolished, reaching less than 0.01% compared to the wild-type strain. Cloning and transfer of the C12-2 cluster to the mNP10 mutant partially restored FFA production, albeit to a low level. The discovery of this rare FFA biosynthesis cluster opens possibilities for detailed characterization of the roles of individual genes and their products in the biosynthesis of FFAs in NP10.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Microbiology",
title = "Genomics-Based Insights Into the Biosynthesis and Unusually High Accumulation of Free Fatty Acids by Streptomyces sp NP10",
volume = "9",
doi = "10.3389/fmicb.2018.01302"
}

Schneider, O., Ilić-Tomić, T., Rueckert, C., Kalinowski, J., Gencić, M. S., Zivković, M. Z., Stanković, N., Radulović, N. S., Vasiljević, B., Nikodinović-Runić, J.,& Zotchev, S. B.. (2018). Genomics-Based Insights Into the Biosynthesis and Unusually High Accumulation of Free Fatty Acids by Streptomyces sp NP10. in Frontiers in Microbiology
Frontiers Media Sa, Lausanne., 9.
https://doi.org/10.3389/fmicb.2018.01302

Schneider O, Ilić-Tomić T, Rueckert C, Kalinowski J, Gencić MS, Zivković MZ, Stanković N, Radulović NS, Vasiljević B, Nikodinović-Runić J, Zotchev SB. Genomics-Based Insights Into the Biosynthesis and Unusually High Accumulation of Free Fatty Acids by Streptomyces sp NP10. in Frontiers in Microbiology. 2018;9.
doi:10.3389/fmicb.2018.01302 .

Schneider, Olha, Ilić-Tomić, Tatjana, Rueckert, Christian, Kalinowski, Joern, Gencić, Marija S., Zivković, Milena Z., Stanković, Nada, Radulović, Niko S., Vasiljević, Branka, Nikodinović-Runić, Jasmina, Zotchev, Sergey B., "Genomics-Based Insights Into the Biosynthesis and Unusually High Accumulation of Free Fatty Acids by Streptomyces sp NP10" in Frontiers in Microbiology, 9 (2018),
https://doi.org/10.3389/fmicb.2018.01302 . .

TY  - JOUR
AU  - Ilić-Tomić, Tatjana
AU  - Gencić, Marija S.
AU  - Zivković, Milena Z.
AU  - Vasiljević, Branka
AU  - Đokić, Lidija
AU  - Nikodinović-Runić, Jasmina
AU  - Radulović, Niko S.
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/875
AB  - Herein, a novel soil bacterium Streptomyces sp. NP10 able to grow outside usual streptomycetes optimum conditions (e.g., at 4 A degrees C, pH 9 and high NaCl concentration), exhibiting atypical hemolytic, DNAse, and cellulolytic activities, is described. This strain produces and excretes into the growth medium large amounts of free long-chain fatty acids (FAs). A concurrent lipidomics study revealed a large structural diversity of FAs with over 50 different n- and branched-chain, (un)saturated, and cyclopropane FAs (C-7-C-30) produced by this strain. Two of these, i-17:0cy9-10 and a-18:0cy9-10, represent new natural products and the first ever identified branched cyclopropane FAs. Both free and bound lipid profiles of Streptomyces sp. NP10 were dominated by saturated branched chain FAs (i-14:0, a-15:0, and i-16:0). Although these free FAs showed only a moderate antimicrobial activity, our results suggest that they could have an ecophysiological role in interspecies signaling with another soil microorganism Pseudomonas aeruginosa. This work represents the first comprehensive report on the structural diversity and complexity of the free FA pool in Streptomyces. A naturally occurring streptomycete, such as Streptomyces sp. NP10, which secretes significant amounts of free long-chain FAs (non-cytotoxic) into the medium, could be useful in microbial biodiesel production.
PB  - Springer, New York
T2  - Applied Microbiology and Biotechnology
T1  - Structural diversity and possible functional roles of free fatty acids of the novel soil isolate Streptomyces sp NP10
EP  - 4833
IS  - 11
SP  - 4815
VL  - 99
DO  - 10.1007/s00253-014-6364-5
ER  - 

@article{
author = "Ilić-Tomić, Tatjana and Gencić, Marija S. and Zivković, Milena Z. and Vasiljević, Branka and Đokić, Lidija and Nikodinović-Runić, Jasmina and Radulović, Niko S.",
year = "2015",
abstract = "Herein, a novel soil bacterium Streptomyces sp. NP10 able to grow outside usual streptomycetes optimum conditions (e.g., at 4 A degrees C, pH 9 and high NaCl concentration), exhibiting atypical hemolytic, DNAse, and cellulolytic activities, is described. This strain produces and excretes into the growth medium large amounts of free long-chain fatty acids (FAs). A concurrent lipidomics study revealed a large structural diversity of FAs with over 50 different n- and branched-chain, (un)saturated, and cyclopropane FAs (C-7-C-30) produced by this strain. Two of these, i-17:0cy9-10 and a-18:0cy9-10, represent new natural products and the first ever identified branched cyclopropane FAs. Both free and bound lipid profiles of Streptomyces sp. NP10 were dominated by saturated branched chain FAs (i-14:0, a-15:0, and i-16:0). Although these free FAs showed only a moderate antimicrobial activity, our results suggest that they could have an ecophysiological role in interspecies signaling with another soil microorganism Pseudomonas aeruginosa. This work represents the first comprehensive report on the structural diversity and complexity of the free FA pool in Streptomyces. A naturally occurring streptomycete, such as Streptomyces sp. NP10, which secretes significant amounts of free long-chain FAs (non-cytotoxic) into the medium, could be useful in microbial biodiesel production.",
publisher = "Springer, New York",
journal = "Applied Microbiology and Biotechnology",
title = "Structural diversity and possible functional roles of free fatty acids of the novel soil isolate Streptomyces sp NP10",
pages = "4833-4815",
number = "11",
volume = "99",
doi = "10.1007/s00253-014-6364-5"
}

Ilić-Tomić, T., Gencić, M. S., Zivković, M. Z., Vasiljević, B., Đokić, L., Nikodinović-Runić, J.,& Radulović, N. S.. (2015). Structural diversity and possible functional roles of free fatty acids of the novel soil isolate Streptomyces sp NP10. in Applied Microbiology and Biotechnology
Springer, New York., 99(11), 4815-4833.
https://doi.org/10.1007/s00253-014-6364-5

Ilić-Tomić T, Gencić MS, Zivković MZ, Vasiljević B, Đokić L, Nikodinović-Runić J, Radulović NS. Structural diversity and possible functional roles of free fatty acids of the novel soil isolate Streptomyces sp NP10. in Applied Microbiology and Biotechnology. 2015;99(11):4815-4833.
doi:10.1007/s00253-014-6364-5 .

Ilić-Tomić, Tatjana, Gencić, Marija S., Zivković, Milena Z., Vasiljević, Branka, Đokić, Lidija, Nikodinović-Runić, Jasmina, Radulović, Niko S., "Structural diversity and possible functional roles of free fatty acids of the novel soil isolate Streptomyces sp NP10" in Applied Microbiology and Biotechnology, 99, no. 11 (2015):4815-4833,
https://doi.org/10.1007/s00253-014-6364-5 . .

TY  - JOUR
AU  - Radulović, Niko S.
AU  - Zlatković, Dragan B.
AU  - Ilić-Tomić, Tatjana
AU  - Šenerović, Lidija
AU  - Nikodinović-Runić, Jasmina
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/724
AB  - Ethnopharmacological relevance: Reseda lutea L (Resedaceae) or Wild Mignonette is a widely distributed plant species. Pliny the Elder (AD 23-AD 79), a Roman scholar and naturalist, reported the use of R. lutea for reducing tumors in his Historia naturalis. Accounts of the beneficial effects of R. lutea in tumor treatment could also be found in the works of later authors, such as Etienne Francois Geoffroy (1672-1731) and Samuel Frederick Gray (1766-1828). However, to date no in vivo or in vitro evidence exists in support of the alleged tumor healing properties of R. lutea. Materials and methods: The composition of autolysates obtained from different organs (root, flower and fruit) of R. lutea was investigated by GC and GC-MS analyses and IR, 1D and 2D NMR spectroscopy. These analyses led to the discovery of a new compound isolated in pure form from the flower autolysate. Autolysates and their major constituents were submitted to MU-dye reduction cytotoxic assay on human A375 (melanoma) and MRC5 (fibroblast) cell lines. Mechanism of the cytotoxic effects was studied by cell cycle analysis and Annexin V assay. Results: Benzyl isothiocyanate and 2-(alpha-L-rhamnopyranosyloxy)benzyl isothiocyanate were identified as the major constituents of the root and flower autolysates, respectively (the later represents a new natural product). These compounds showed significant antiproliferative effects against both cell lines, which could also explain the observed high cytotoxic activity of the tested autolysates. Cell cycle analysis revealed apoptosis as the probable mechanism of cell death. Conclusions: Tumor healing properties attributed to R. lutea in the pre-modern texts were substantiated by the herein obtained results. Two isothiocyanates were found to be the major carriers of the observed activity. Although there was a relatively low differential effect of the plant metabolites on transformed and non-transformed cell lines, one can argue that the noted strong cytotoxicity provides first evidence that could explain the long forgotten use of this particular species.
PB  - Elsevier Ireland Ltd, Clare
T2  - Journal of Ethnopharmacology
T1  - Cytotoxic effect of Reseda lutea L.: A case of forgotten remedy
EP  - 132
IS  - 1
SP  - 125
VL  - 153
DO  - 10.1016/j.jep.2014.01.034
ER  - 

@article{
author = "Radulović, Niko S. and Zlatković, Dragan B. and Ilić-Tomić, Tatjana and Šenerović, Lidija and Nikodinović-Runić, Jasmina",
year = "2014",
abstract = "Ethnopharmacological relevance: Reseda lutea L (Resedaceae) or Wild Mignonette is a widely distributed plant species. Pliny the Elder (AD 23-AD 79), a Roman scholar and naturalist, reported the use of R. lutea for reducing tumors in his Historia naturalis. Accounts of the beneficial effects of R. lutea in tumor treatment could also be found in the works of later authors, such as Etienne Francois Geoffroy (1672-1731) and Samuel Frederick Gray (1766-1828). However, to date no in vivo or in vitro evidence exists in support of the alleged tumor healing properties of R. lutea. Materials and methods: The composition of autolysates obtained from different organs (root, flower and fruit) of R. lutea was investigated by GC and GC-MS analyses and IR, 1D and 2D NMR spectroscopy. These analyses led to the discovery of a new compound isolated in pure form from the flower autolysate. Autolysates and their major constituents were submitted to MU-dye reduction cytotoxic assay on human A375 (melanoma) and MRC5 (fibroblast) cell lines. Mechanism of the cytotoxic effects was studied by cell cycle analysis and Annexin V assay. Results: Benzyl isothiocyanate and 2-(alpha-L-rhamnopyranosyloxy)benzyl isothiocyanate were identified as the major constituents of the root and flower autolysates, respectively (the later represents a new natural product). These compounds showed significant antiproliferative effects against both cell lines, which could also explain the observed high cytotoxic activity of the tested autolysates. Cell cycle analysis revealed apoptosis as the probable mechanism of cell death. Conclusions: Tumor healing properties attributed to R. lutea in the pre-modern texts were substantiated by the herein obtained results. Two isothiocyanates were found to be the major carriers of the observed activity. Although there was a relatively low differential effect of the plant metabolites on transformed and non-transformed cell lines, one can argue that the noted strong cytotoxicity provides first evidence that could explain the long forgotten use of this particular species.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Journal of Ethnopharmacology",
title = "Cytotoxic effect of Reseda lutea L.: A case of forgotten remedy",
pages = "132-125",
number = "1",
volume = "153",
doi = "10.1016/j.jep.2014.01.034"
}

Radulović, N. S., Zlatković, D. B., Ilić-Tomić, T., Šenerović, L.,& Nikodinović-Runić, J.. (2014). Cytotoxic effect of Reseda lutea L.: A case of forgotten remedy. in Journal of Ethnopharmacology
Elsevier Ireland Ltd, Clare., 153(1), 125-132.
https://doi.org/10.1016/j.jep.2014.01.034

Radulović NS, Zlatković DB, Ilić-Tomić T, Šenerović L, Nikodinović-Runić J. Cytotoxic effect of Reseda lutea L.: A case of forgotten remedy. in Journal of Ethnopharmacology. 2014;153(1):125-132.
doi:10.1016/j.jep.2014.01.034 .

Radulović, Niko S., Zlatković, Dragan B., Ilić-Tomić, Tatjana, Šenerović, Lidija, Nikodinović-Runić, Jasmina, "Cytotoxic effect of Reseda lutea L.: A case of forgotten remedy" in Journal of Ethnopharmacology, 153, no. 1 (2014):125-132,
https://doi.org/10.1016/j.jep.2014.01.034 . .

TY  - JOUR
AU  - Radulović, Niko S.
AU  - Mladenović, Marko Z.
AU  - Blagojević, Polina D.
AU  - Stojanović-Radić, Zorica Z.
AU  - Ilić-Tomić, Tatjana
AU  - Šenerović, Lidija
AU  - Nikodinović-Runić, Jasmina
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/694
AB  - To determine the exact structure of previously tentatively identified minor essential-oil constituents of a Chamomile species (Antemis segetalis Ten. (Asteraceae)), we have synthesized a small combinatorial library of 54 regioisomeric allylmethoxyphenyl pentanoates and 2-pentenoates (49 completely new compounds). GC-MS in combination with 1D- and 2D-NMR analyses of the library compounds provided unambiguous data that led to a straightforward identification of the mentioned A. segetalis constituents as eugenyl angelate, 2-methylbutanoate and 3-methylbutanoate (0.21, 0.22, and 0.13 mg/100 g of fresh plant material, respectively). To assess the safety and potential beneficial pharmacological uses of these naturally occurring esters and several other library compounds (these were tested to provide relevant data for a SAR (structure-activity relationship) analysis), we have studied the effect of these compounds in several models of toxicity (acute toxicity against Artemia sauna, cytotoxicity against two cell lines (fibroblast and melanoma)), as well as their acetylcholinesterase inhibitory and antibacterial activities. Anthemis segetalis constituents showed low to moderate activity in all tests. The obtained results suggest that the intake of these compounds in naturally available amounts, on their own, would probably not represent a risk to human health but the possible adverse interactions with the plant matrix should not be neglected.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Food and Chemical Toxicology
T1  - Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.)
EP  - 565
SP  - 554
VL  - 62
DO  - 10.1016/j.fct.2013.09.017
ER  - 

@article{
author = "Radulović, Niko S. and Mladenović, Marko Z. and Blagojević, Polina D. and Stojanović-Radić, Zorica Z. and Ilić-Tomić, Tatjana and Šenerović, Lidija and Nikodinović-Runić, Jasmina",
year = "2013",
abstract = "To determine the exact structure of previously tentatively identified minor essential-oil constituents of a Chamomile species (Antemis segetalis Ten. (Asteraceae)), we have synthesized a small combinatorial library of 54 regioisomeric allylmethoxyphenyl pentanoates and 2-pentenoates (49 completely new compounds). GC-MS in combination with 1D- and 2D-NMR analyses of the library compounds provided unambiguous data that led to a straightforward identification of the mentioned A. segetalis constituents as eugenyl angelate, 2-methylbutanoate and 3-methylbutanoate (0.21, 0.22, and 0.13 mg/100 g of fresh plant material, respectively). To assess the safety and potential beneficial pharmacological uses of these naturally occurring esters and several other library compounds (these were tested to provide relevant data for a SAR (structure-activity relationship) analysis), we have studied the effect of these compounds in several models of toxicity (acute toxicity against Artemia sauna, cytotoxicity against two cell lines (fibroblast and melanoma)), as well as their acetylcholinesterase inhibitory and antibacterial activities. Anthemis segetalis constituents showed low to moderate activity in all tests. The obtained results suggest that the intake of these compounds in naturally available amounts, on their own, would probably not represent a risk to human health but the possible adverse interactions with the plant matrix should not be neglected.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Food and Chemical Toxicology",
title = "Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.)",
pages = "565-554",
volume = "62",
doi = "10.1016/j.fct.2013.09.017"
}

Radulović, N. S., Mladenović, M. Z., Blagojević, P. D., Stojanović-Radić, Z. Z., Ilić-Tomić, T., Šenerović, L.,& Nikodinović-Runić, J.. (2013). Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.). in Food and Chemical Toxicology
Pergamon-Elsevier Science Ltd, Oxford., 62, 554-565.
https://doi.org/10.1016/j.fct.2013.09.017

Radulović NS, Mladenović MZ, Blagojević PD, Stojanović-Radić ZZ, Ilić-Tomić T, Šenerović L, Nikodinović-Runić J. Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.). in Food and Chemical Toxicology. 2013;62:554-565.
doi:10.1016/j.fct.2013.09.017 .

Radulović, Niko S., Mladenović, Marko Z., Blagojević, Polina D., Stojanović-Radić, Zorica Z., Ilić-Tomić, Tatjana, Šenerović, Lidija, Nikodinović-Runić, Jasmina, "Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.)" in Food and Chemical Toxicology, 62 (2013):554-565,
https://doi.org/10.1016/j.fct.2013.09.017 . .