Computational design, synthesis and biological evaluation of new heterocyclic compounds as selective tumorogenesis inhibitors

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Computational design, synthesis and biological evaluation of new heterocyclic compounds as selective tumorogenesis inhibitors (en)
Компјутерско дизајнирање, синтеза и биолошка евалуација нових хетероцикличних једињења као селективних инхибитора туморогенезе (sr)
Kompjutersko dizajniranje, sinteza i biološka evaluacija novih heterocikličnih jedinjenja kao selektivnih inhibitora tumorogeneze (sr_RS)
Authors

Publications

Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans

Jovanović, Milos; Milovanović, Jelena; O'Connor, Kevin; Blagojević, Stevan; Begović, Biljana ; Lukić, Vera; Nikodinović-Runić, Jasmina; Savić, Vladimir

(Academic Press Inc Elsevier Science, San Diego, 2019)

TY  - JOUR
AU  - Jovanović, Milos
AU  - Milovanović, 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://imagine.imgge.bg.ac.rs/handle/123456789/1258
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
EP  - 217
SP  - 209
VL  - 87
DO  - 10.1016/j.bioorg.2019.03.023
ER  - 
@article{
author = "Jovanović, Milos and Milovanović, 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",
pages = "217-209",
volume = "87",
doi = "10.1016/j.bioorg.2019.03.023"
}
Jovanović, M., Milovanović, 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, Milovanović 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, Milos, Milovanović, 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 . .
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Anti-biofilm Properties of Bacterial Di-Rhamnolipids and Their Semi-Synthetic Amide Derivatives

Aleksić, Ivana; Petković, Milos; Jovanović, Milos; Milivojević, Dušan; Vasiljević, Branka; Nikodinović-Runić, Jasmina; Šenerović, Lidija

(Frontiers Media Sa, Lausanne, 2017)

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Petković, Milos
AU  - Jovanović, Milos
AU  - Milivojević, Dušan
AU  - Vasiljević, Branka
AU  - Nikodinović-Runić, Jasmina
AU  - Šenerović, Lidija
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1033
AB  - A new strain, namely Lysinibacillus sp. BV152.1 was isolated from the rhizosphere of ground ivy (Glechoma hederacea L.) producing metabolites with potent ability to inhibit biofilm formation of an important human pathogens Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and Serratia marcescens. Structural characterization revealed di-rhamnolipids mixture containing rhamnose (Rha)-Rha-C10-C10, Rha-Rha-C8-C10, and Rha-Rha-C10-C12 in the ratio 7: 2: 1 as the active principle. Purified di-rhamnolipids, as well as commercially available di-rhamnolipids (Rha-Rha-C10-C10, 93%) were used as the substrate for the chemical derivatization for the first time, yielding three semisynthetic amide derivatives, benzyl-, piperidine-, and morpholine. A comparative study of the anti-biofilm, antibacterial and cytotoxic properties revealed that di-Rha from Lysinibacillus sp. BV152.1 were more potent in biofilm inhibition, both cell adhesion and biofilm maturation, than commercial di-rhamnolipids inhibiting 50% of P. aeruginosa PAO1 biofilm formation at 50 mu g mL(-1) and 75 mu g mL(-1), respectively. None of the dirhamnolipids exhibited antimicrobial properties at concentrations of up to 500 mu g mL(-1). Amide derivatization improved inhibition of biofilm formation and dispersion activities of di-rhamnolipids from both sources, with morpholine derivative being the most active causing more than 80% biofilm inhibition at concentrations 100 mu g mL(-1). Semisynthetic amide derivatives showed increased antibacterial activity against S. aureus, and also showed higher cytotoxicity. Therefore, described di-rhamnolipids are potent anti-biofilm agents and the described approach can be seen as viable approach in reaching new rhamnolipid based derivatives with tailored biological properties.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Microbiology
T1  - Anti-biofilm Properties of Bacterial Di-Rhamnolipids and Their Semi-Synthetic Amide Derivatives
VL  - 8
DO  - 10.3389/fmicb.2017.02454
ER  - 
@article{
author = "Aleksić, Ivana and Petković, Milos and Jovanović, Milos and Milivojević, Dušan and Vasiljević, Branka and Nikodinović-Runić, Jasmina and Šenerović, Lidija",
year = "2017",
abstract = "A new strain, namely Lysinibacillus sp. BV152.1 was isolated from the rhizosphere of ground ivy (Glechoma hederacea L.) producing metabolites with potent ability to inhibit biofilm formation of an important human pathogens Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and Serratia marcescens. Structural characterization revealed di-rhamnolipids mixture containing rhamnose (Rha)-Rha-C10-C10, Rha-Rha-C8-C10, and Rha-Rha-C10-C12 in the ratio 7: 2: 1 as the active principle. Purified di-rhamnolipids, as well as commercially available di-rhamnolipids (Rha-Rha-C10-C10, 93%) were used as the substrate for the chemical derivatization for the first time, yielding three semisynthetic amide derivatives, benzyl-, piperidine-, and morpholine. A comparative study of the anti-biofilm, antibacterial and cytotoxic properties revealed that di-Rha from Lysinibacillus sp. BV152.1 were more potent in biofilm inhibition, both cell adhesion and biofilm maturation, than commercial di-rhamnolipids inhibiting 50% of P. aeruginosa PAO1 biofilm formation at 50 mu g mL(-1) and 75 mu g mL(-1), respectively. None of the dirhamnolipids exhibited antimicrobial properties at concentrations of up to 500 mu g mL(-1). Amide derivatization improved inhibition of biofilm formation and dispersion activities of di-rhamnolipids from both sources, with morpholine derivative being the most active causing more than 80% biofilm inhibition at concentrations 100 mu g mL(-1). Semisynthetic amide derivatives showed increased antibacterial activity against S. aureus, and also showed higher cytotoxicity. Therefore, described di-rhamnolipids are potent anti-biofilm agents and the described approach can be seen as viable approach in reaching new rhamnolipid based derivatives with tailored biological properties.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Microbiology",
title = "Anti-biofilm Properties of Bacterial Di-Rhamnolipids and Their Semi-Synthetic Amide Derivatives",
volume = "8",
doi = "10.3389/fmicb.2017.02454"
}
Aleksić, I., Petković, M., Jovanović, M., Milivojević, D., Vasiljević, B., Nikodinović-Runić, J.,& Šenerović, L.. (2017). Anti-biofilm Properties of Bacterial Di-Rhamnolipids and Their Semi-Synthetic Amide Derivatives. in Frontiers in Microbiology
Frontiers Media Sa, Lausanne., 8.
https://doi.org/10.3389/fmicb.2017.02454
Aleksić I, Petković M, Jovanović M, Milivojević D, Vasiljević B, Nikodinović-Runić J, Šenerović L. Anti-biofilm Properties of Bacterial Di-Rhamnolipids and Their Semi-Synthetic Amide Derivatives. in Frontiers in Microbiology. 2017;8.
doi:10.3389/fmicb.2017.02454 .
Aleksić, Ivana, Petković, Milos, Jovanović, Milos, Milivojević, Dušan, Vasiljević, Branka, Nikodinović-Runić, Jasmina, Šenerović, Lidija, "Anti-biofilm Properties of Bacterial Di-Rhamnolipids and Their Semi-Synthetic Amide Derivatives" in Frontiers in Microbiology, 8 (2017),
https://doi.org/10.3389/fmicb.2017.02454 . .
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Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies

Simić, Milena; Paunović, Nikola; Borić, Ivan; Randjelović, Jelena; Vojnović, Sandra; Nikodinović-Runić, Jasmina; Pekmezović, Marina; Savić, Vladimir

(Pergamon-Elsevier Science Ltd, Oxford, 2016)

TY  - JOUR
AU  - Simić, Milena
AU  - Paunović, Nikola
AU  - Borić, Ivan
AU  - Randjelović, Jelena
AU  - Vojnović, Sandra
AU  - Nikodinović-Runić, Jasmina
AU  - Pekmezović, Marina
AU  - Savić, Vladimir
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/971
AB  - A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & Medicinal Chemistry Letters
T1  - Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies
EP  - 239
IS  - 1
SP  - 235
VL  - 26
DO  - 10.1016/j.bmcl.2015.08.086
ER  - 
@article{
author = "Simić, Milena and Paunović, Nikola and Borić, Ivan and Randjelović, Jelena and Vojnović, Sandra and Nikodinović-Runić, Jasmina and Pekmezović, Marina and Savić, Vladimir",
year = "2016",
abstract = "A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & Medicinal Chemistry Letters",
title = "Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies",
pages = "239-235",
number = "1",
volume = "26",
doi = "10.1016/j.bmcl.2015.08.086"
}
Simić, M., Paunović, N., Borić, I., Randjelović, J., Vojnović, S., Nikodinović-Runić, J., Pekmezović, M.,& Savić, V.. (2016). Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies. in Bioorganic & Medicinal Chemistry Letters
Pergamon-Elsevier Science Ltd, Oxford., 26(1), 235-239.
https://doi.org/10.1016/j.bmcl.2015.08.086
Simić M, Paunović N, Borić I, Randjelović J, Vojnović S, Nikodinović-Runić J, Pekmezović M, Savić V. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies. in Bioorganic & Medicinal Chemistry Letters. 2016;26(1):235-239.
doi:10.1016/j.bmcl.2015.08.086 .
Simić, Milena, Paunović, Nikola, Borić, Ivan, Randjelović, Jelena, Vojnović, Sandra, Nikodinović-Runić, Jasmina, Pekmezović, Marina, Savić, Vladimir, "Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies" in Bioorganic & Medicinal Chemistry Letters, 26, no. 1 (2016):235-239,
https://doi.org/10.1016/j.bmcl.2015.08.086 . .
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Chemoselective biocatalytic reduction of conjugated nitroalkenes: New application for an Escherichia coli BL21(DE3) expression strain

Jovanović, Predrag; Jeremić, Sanja; Đokić, Lidija; Savić, Vladimir; Milovanović, Jelena; Maslak, Veselin; Ivković, Branka; Vasiljević, Branka; Nikodinović-Runić, Jasmina

(Elsevier Science Inc, New York, 2014)

TY  - JOUR
AU  - Jovanović, Predrag
AU  - Jeremić, Sanja
AU  - Đokić, Lidija
AU  - Savić, Vladimir
AU  - Milovanović, Jelena
AU  - Maslak, Veselin
AU  - Ivković, Branka
AU  - Vasiljević, Branka
AU  - Nikodinović-Runić, Jasmina
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/716
AB  - Chemoselective reduction of activated carbon-carbon double bond in conjugated nitroalkenes was achieved using Escherichia coli BL21(DE3) whole cells. Nine different substrates have been used furnishing the reduced products in moderate to good yields. 1-Nitro-4-phenyl-1,3-butadiene and (2-nitro-1-propenyl)benzene were successfully biotransformed with corresponding product yields of 54% and 45% respectively. Using this simple and environmentally friendly system 2-(2-nitropropyl)pyridine and 2-(2-nitropropyl)naphthalene were synthesized and characterized for the first time. High substrate conversion efficiency was coupled with low enantioselectivity, however 29% enantiomeric excess was detected in the case of 2-(2-nitropropyl)pyridine. It was shown that electronic properties of the aromatic ring, which affected polarity of the double bond, were not highly influential factors in the reduction process, but the presence of the nitro functionality was essential for the reaction to proceed. 1-Phenyl-4-nitro-1,3-butadiene could not be biotransformed by whole cells of Pseudomonas putida KT2440 or Bacillus subtilis 168 while it was successfully reduced by E. coli DH5 alpha but with lower efficiency in comparison to E. coli BL21(DE3). Knockout mutant affected in nemA gene coding for N-ethylmaleimide reductase (BL21 Delta nemA) could still catalyze bioreductions suggesting multiple active reductases within E. coli BL21(DE3) biocatalyst. The described biocatalytic reduction of substituted nitroalkenes provides an efficient route for the preparation of the corresponding nitroalkanes and introduces the new application of the strain traditionally utilized for recombinant protein expression.
PB  - Elsevier Science Inc, New York
T2  - Enzyme and Microbial Technology
T1  - Chemoselective biocatalytic reduction of conjugated nitroalkenes: New application for an Escherichia coli BL21(DE3) expression strain
EP  - 23
SP  - 16
VL  - 60
DO  - 10.1016/j.enzmictec.2014.03.010
ER  - 
@article{
author = "Jovanović, Predrag and Jeremić, Sanja and Đokić, Lidija and Savić, Vladimir and Milovanović, Jelena and Maslak, Veselin and Ivković, Branka and Vasiljević, Branka and Nikodinović-Runić, Jasmina",
year = "2014",
abstract = "Chemoselective reduction of activated carbon-carbon double bond in conjugated nitroalkenes was achieved using Escherichia coli BL21(DE3) whole cells. Nine different substrates have been used furnishing the reduced products in moderate to good yields. 1-Nitro-4-phenyl-1,3-butadiene and (2-nitro-1-propenyl)benzene were successfully biotransformed with corresponding product yields of 54% and 45% respectively. Using this simple and environmentally friendly system 2-(2-nitropropyl)pyridine and 2-(2-nitropropyl)naphthalene were synthesized and characterized for the first time. High substrate conversion efficiency was coupled with low enantioselectivity, however 29% enantiomeric excess was detected in the case of 2-(2-nitropropyl)pyridine. It was shown that electronic properties of the aromatic ring, which affected polarity of the double bond, were not highly influential factors in the reduction process, but the presence of the nitro functionality was essential for the reaction to proceed. 1-Phenyl-4-nitro-1,3-butadiene could not be biotransformed by whole cells of Pseudomonas putida KT2440 or Bacillus subtilis 168 while it was successfully reduced by E. coli DH5 alpha but with lower efficiency in comparison to E. coli BL21(DE3). Knockout mutant affected in nemA gene coding for N-ethylmaleimide reductase (BL21 Delta nemA) could still catalyze bioreductions suggesting multiple active reductases within E. coli BL21(DE3) biocatalyst. The described biocatalytic reduction of substituted nitroalkenes provides an efficient route for the preparation of the corresponding nitroalkanes and introduces the new application of the strain traditionally utilized for recombinant protein expression.",
publisher = "Elsevier Science Inc, New York",
journal = "Enzyme and Microbial Technology",
title = "Chemoselective biocatalytic reduction of conjugated nitroalkenes: New application for an Escherichia coli BL21(DE3) expression strain",
pages = "23-16",
volume = "60",
doi = "10.1016/j.enzmictec.2014.03.010"
}
Jovanović, P., Jeremić, S., Đokić, L., Savić, V., Milovanović, J., Maslak, V., Ivković, B., Vasiljević, B.,& Nikodinović-Runić, J.. (2014). Chemoselective biocatalytic reduction of conjugated nitroalkenes: New application for an Escherichia coli BL21(DE3) expression strain. in Enzyme and Microbial Technology
Elsevier Science Inc, New York., 60, 16-23.
https://doi.org/10.1016/j.enzmictec.2014.03.010
Jovanović P, Jeremić S, Đokić L, Savić V, Milovanović J, Maslak V, Ivković B, Vasiljević B, Nikodinović-Runić J. Chemoselective biocatalytic reduction of conjugated nitroalkenes: New application for an Escherichia coli BL21(DE3) expression strain. in Enzyme and Microbial Technology. 2014;60:16-23.
doi:10.1016/j.enzmictec.2014.03.010 .
Jovanović, Predrag, Jeremić, Sanja, Đokić, Lidija, Savić, Vladimir, Milovanović, Jelena, Maslak, Veselin, Ivković, Branka, Vasiljević, Branka, Nikodinović-Runić, Jasmina, "Chemoselective biocatalytic reduction of conjugated nitroalkenes: New application for an Escherichia coli BL21(DE3) expression strain" in Enzyme and Microbial Technology, 60 (2014):16-23,
https://doi.org/10.1016/j.enzmictec.2014.03.010 . .
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Highly efficient Michael-type addition of acetaldehyde to beta-nitrostyrenes by whole resting cells of Escherichia coli expressing 4-oxalocrotonate tautomerase

Narancić, Tanja; Milovanović, Jelena; Jovanović, Predrag; Francuski, Djordje; Bigović, Miljan; Maslak, Veselin; Savić, Vladimir; Vasiljević, Branka; O'Connor, Kevin ; Nikodinović-Runić, Jasmina

(Elsevier Sci Ltd, Oxford, 2013)

TY  - JOUR
AU  - Narancić, Tanja
AU  - Milovanović, Jelena
AU  - Jovanović, Predrag
AU  - Francuski, Djordje
AU  - Bigović, Miljan
AU  - Maslak, Veselin
AU  - Savić, Vladimir
AU  - Vasiljević, Branka
AU  - O'Connor, Kevin 
AU  - Nikodinović-Runić, Jasmina
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/656
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 ( gt 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
EP  - 468
SP  - 462
VL  - 142
DO  - 10.1016/j.biortech.2013.05.074
ER  - 
@article{
author = "Narancić, Tanja and Milovanović, Jelena and Jovanović, Predrag and Francuski, Djordje 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 ( gt 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",
pages = "468-462",
volume = "142",
doi = "10.1016/j.biortech.2013.05.074"
}
Narancić, T., Milovanović, J., Jovanović, P., Francuski, D., 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, Milovanović J, Jovanović P, Francuski D, 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, Milovanović, Jelena, Jovanović, Predrag, Francuski, Djordje, 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 . .
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