TY  - JOUR
AU  - Jovanović, Miloš
AU  - Radivojević, Jelena
AU  - O'Connor, Kevin
AU  - Blagojević, Stevan
AU  - Begović, Biljana
AU  - Lukić, Vera
AU  - Nikodinović-Runić, Jasmina
AU  - Savić, Vladimir
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3335
AB  - Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 mu g/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Bioorganic Chemistry
T1  - Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans
VL  - 87
SP  - 209
EP  - 217
DO  - 10.1016/j.bioorg.2019.03.023
ER  - 

@article{
author = "Jovanović, Miloš and Radivojević, Jelena and O'Connor, Kevin and Blagojević, Stevan and Begović, Biljana and Lukić, Vera and Nikodinović-Runić, Jasmina and Savić, Vladimir",
year = "2019",
abstract = "Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 mu g/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Bioorganic Chemistry",
title = "Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans",
volume = "87",
pages = "209-217",
doi = "10.1016/j.bioorg.2019.03.023"
}

Jovanović, M., Radivojević, J., O'Connor, K., Blagojević, S., Begović, B., Lukić, V., Nikodinović-Runić, J.,& Savić, V.. (2019). Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans. in Bioorganic Chemistry
Academic Press Inc Elsevier Science, San Diego., 87, 209-217.
https://doi.org/10.1016/j.bioorg.2019.03.023

Jovanović M, Radivojević J, O'Connor K, Blagojević S, Begović B, Lukić V, Nikodinović-Runić J, Savić V. Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans. in Bioorganic Chemistry. 2019;87:209-217.
doi:10.1016/j.bioorg.2019.03.023 .

Jovanović, Miloš, Radivojević, Jelena, O'Connor, Kevin, Blagojević, Stevan, Begović, Biljana, Lukić, Vera, Nikodinović-Runić, Jasmina, Savić, Vladimir, "Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans" in Bioorganic Chemistry, 87 (2019):209-217,
https://doi.org/10.1016/j.bioorg.2019.03.023 . .

TY  - JOUR
AU  - Radivojević, Jelena
AU  - Minovska, Gordana
AU  - Senerović, Lidija
AU  - O'Connor, Kevin
AU  - Jovanović, Predrag
AU  - Savić, Vladimir
AU  - Tokić-Vujošević, Zorana
AU  - Nikodinović-Runić, Jasmina
AU  - Maslak, Veselin
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2107
AB  - Synthesis of gamma-nitroaldehydes from branched chain aldehydes and a range of alpha,beta-unsaturated nitroalkenes was achieved by a whole-cell biocatalytic reaction using 4-oxalocrotonate tautomerase as catalyst. Under mild conditions, cyclic and acyclic branched aldehydes were converted into synthetically valuable quaternary carbon containing gamma-nitroaldehydes. The yields of the desired products were influenced by reaction condition parameters such as organic solvent, temperature and pH. The whole-cell biocatalytic approach to the generation of alpha,alpha-substituted gamma-nitroaldehydes was compared to the organocatalytic approach involving the lithium salt of phenylalanine as a catalyst. As the resulting gamma-nitroaldehydes exhibited moderate antifungal activity and mild in vitro cytotoxicity against human fibroblasts (0.2-0.4 mM) they could further be examined as potentially useful pharmaceutical synthons.
PB  - Royal Soc Chemistry, Cambridge
T2  - Russian Journal of Genetics
T1  - Synthesis of gamma-nitroaldehydes containing quaternary carbon in the alpha-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst
VL  - 4
IS  - 105
SP  - 60502
EP  - 60510
DO  - 10.1039/c4ra05517a
ER  - 

@article{
author = "Radivojević, Jelena and Minovska, Gordana and Senerović, Lidija and O'Connor, Kevin and Jovanović, Predrag and Savić, Vladimir and Tokić-Vujošević, Zorana and Nikodinović-Runić, Jasmina and Maslak, Veselin",
year = "2014",
abstract = "Synthesis of gamma-nitroaldehydes from branched chain aldehydes and a range of alpha,beta-unsaturated nitroalkenes was achieved by a whole-cell biocatalytic reaction using 4-oxalocrotonate tautomerase as catalyst. Under mild conditions, cyclic and acyclic branched aldehydes were converted into synthetically valuable quaternary carbon containing gamma-nitroaldehydes. The yields of the desired products were influenced by reaction condition parameters such as organic solvent, temperature and pH. The whole-cell biocatalytic approach to the generation of alpha,alpha-substituted gamma-nitroaldehydes was compared to the organocatalytic approach involving the lithium salt of phenylalanine as a catalyst. As the resulting gamma-nitroaldehydes exhibited moderate antifungal activity and mild in vitro cytotoxicity against human fibroblasts (0.2-0.4 mM) they could further be examined as potentially useful pharmaceutical synthons.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Russian Journal of Genetics",
title = "Synthesis of gamma-nitroaldehydes containing quaternary carbon in the alpha-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst",
volume = "4",
number = "105",
pages = "60502-60510",
doi = "10.1039/c4ra05517a"
}

Radivojević, J., Minovska, G., Senerović, L., O'Connor, K., Jovanović, P., Savić, V., Tokić-Vujošević, Z., Nikodinović-Runić, J.,& Maslak, V.. (2014). Synthesis of gamma-nitroaldehydes containing quaternary carbon in the alpha-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst. in Russian Journal of Genetics
Royal Soc Chemistry, Cambridge., 4(105), 60502-60510.
https://doi.org/10.1039/c4ra05517a

Radivojević J, Minovska G, Senerović L, O'Connor K, Jovanović P, Savić V, Tokić-Vujošević Z, Nikodinović-Runić J, Maslak V. Synthesis of gamma-nitroaldehydes containing quaternary carbon in the alpha-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst. in Russian Journal of Genetics. 2014;4(105):60502-60510.
doi:10.1039/c4ra05517a .

Radivojević, Jelena, Minovska, Gordana, Senerović, Lidija, O'Connor, Kevin, Jovanović, Predrag, Savić, Vladimir, Tokić-Vujošević, Zorana, Nikodinović-Runić, Jasmina, Maslak, Veselin, "Synthesis of gamma-nitroaldehydes containing quaternary carbon in the alpha-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst" in Russian Journal of Genetics, 4, no. 105 (2014):60502-60510,
https://doi.org/10.1039/c4ra05517a . .

TY  - JOUR
AU  - Narancić, Tanja
AU  - Kadivojević, Jelena
AU  - Jovanović, Predrag
AU  - Francuski, Đorđe
AU  - Bigović, Miljan
AU  - Maslak, Veselin
AU  - Savić, Vladimir
AU  - Vasiljević, Branka
AU  - O'Connor, Kevin
AU  - Nikodinović-Runić, Jasmina
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1960
AB  - A novel whole cell system based on recombinantly expressed 4-oxalocrotonate tautomerase (4-OT) was developed and shown to be an effective biocatalyst for the asymmetric Michael addition of acetaldehyde to beta-nitrostyrenes. Optimal ratio of substrates (2 mM beta-nitrostyrenes and 20 mM acetaldehyde) and biocatalyst of 5 g of cell dry weight of biocatalyst per liter was determined. Through further bioprocess improvement by sequential addition of substrate 10 mM nitrostyrene biotransformation was achieved within 150 min. Excellent enantioselectivity (>99% ee) and product yields of up to 60% were obtained with beta-nitrostyrene substrate. The biotransformation product, 4-nitro-3-phenyl-butanal, was isolated from aqueous media and further transformed into the corresponding amino alcohol. The biocatalyst exhibited lower reaction rates with p-Cl-, o-Cl- and p-F-beta-nitrostyrenes with product yields of 38%, 51%, 31% and ee values of 84%, 88% and 94% respectively. The importance of the terminal,proline of 4-UT was confirmed by two proline enriched variants and homology modeling.
PB  - Elsevier Sci Ltd, Oxford
T2  - Bioresource Technology
T1  - Highly efficient Michael-type addition of acetaldehyde to beta-nitrostyrenes by whole resting cells of Escherichia coli expressing 4-oxalocrotonate tautomerase
VL  - 142
SP  - 462
EP  - 468
DO  - 10.1016/j.biortech.2013.05.074
ER  - 

@article{
author = "Narancić, Tanja and Kadivojević, Jelena and Jovanović, Predrag and Francuski, Đorđe and Bigović, Miljan and Maslak, Veselin and Savić, Vladimir and Vasiljević, Branka and O'Connor, Kevin and Nikodinović-Runić, Jasmina",
year = "2013",
abstract = "A novel whole cell system based on recombinantly expressed 4-oxalocrotonate tautomerase (4-OT) was developed and shown to be an effective biocatalyst for the asymmetric Michael addition of acetaldehyde to beta-nitrostyrenes. Optimal ratio of substrates (2 mM beta-nitrostyrenes and 20 mM acetaldehyde) and biocatalyst of 5 g of cell dry weight of biocatalyst per liter was determined. Through further bioprocess improvement by sequential addition of substrate 10 mM nitrostyrene biotransformation was achieved within 150 min. Excellent enantioselectivity (>99% ee) and product yields of up to 60% were obtained with beta-nitrostyrene substrate. The biotransformation product, 4-nitro-3-phenyl-butanal, was isolated from aqueous media and further transformed into the corresponding amino alcohol. The biocatalyst exhibited lower reaction rates with p-Cl-, o-Cl- and p-F-beta-nitrostyrenes with product yields of 38%, 51%, 31% and ee values of 84%, 88% and 94% respectively. The importance of the terminal,proline of 4-UT was confirmed by two proline enriched variants and homology modeling.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Bioresource Technology",
title = "Highly efficient Michael-type addition of acetaldehyde to beta-nitrostyrenes by whole resting cells of Escherichia coli expressing 4-oxalocrotonate tautomerase",
volume = "142",
pages = "462-468",
doi = "10.1016/j.biortech.2013.05.074"
}

Narancić, T., Kadivojević, J., Jovanović, P., Francuski, Đ., Bigović, M., Maslak, V., Savić, V., Vasiljević, B., O'Connor, K.,& Nikodinović-Runić, J.. (2013). Highly efficient Michael-type addition of acetaldehyde to beta-nitrostyrenes by whole resting cells of Escherichia coli expressing 4-oxalocrotonate tautomerase. in Bioresource Technology
Elsevier Sci Ltd, Oxford., 142, 462-468.
https://doi.org/10.1016/j.biortech.2013.05.074

Narancić T, Kadivojević J, Jovanović P, Francuski Đ, Bigović M, Maslak V, Savić V, Vasiljević B, O'Connor K, Nikodinović-Runić J. Highly efficient Michael-type addition of acetaldehyde to beta-nitrostyrenes by whole resting cells of Escherichia coli expressing 4-oxalocrotonate tautomerase. in Bioresource Technology. 2013;142:462-468.
doi:10.1016/j.biortech.2013.05.074 .

Narancić, Tanja, Kadivojević, Jelena, Jovanović, Predrag, Francuski, Đorđe, Bigović, Miljan, Maslak, Veselin, Savić, Vladimir, Vasiljević, Branka, O'Connor, Kevin, Nikodinović-Runić, Jasmina, "Highly efficient Michael-type addition of acetaldehyde to beta-nitrostyrenes by whole resting cells of Escherichia coli expressing 4-oxalocrotonate tautomerase" in Bioresource Technology, 142 (2013):462-468,
https://doi.org/10.1016/j.biortech.2013.05.074 . .