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Optimization and scale-up of liquid-liquid extraction process with ionic liquids (ILs) as a sustainable tool for the separation of the anti-leukemia biopharmaceutical L-asparaginase (ASPase)

Abstract

The development of new biopharmaceuticals for use in new therapies is one of the major drawbacks of the pharmaceutical industry, mainly with the increase of human resistence against the conventional pharmaceutical compounds. In fact, the pharmaceutical industry is facing now the generic drugs growth and, with it, there is a crucial need to minimize the operational costs, mainly enclosing the production and purification steps. This project proposes the use of an alternative and more sustainable purification methodology to separate and isolate an anti-leukemia biopharmaceutical, the L-Asparaginase, from fermented broth. In this context, aqueous two-phase systems (ATPS) composed of Ionic Liquids (ILs) and polymers (polymer-IL, polymer-salt-IL) will be applied. In the first stage of the project, the ATPS will be characterized, with the phase diagrams determination and the respective characterization of their principal thermodynamic properties, as well the developind of simulation models to predict their formation. The second stage contemplates the study of the activity and stability of the commercial ASPase, followed by its extraction at a lab-scale. Having into account the best results obtained in the optimization step described by the second step, in the third stage, the ASPase obtained from the fermented broth of recombinant Pichia pastoris will be purified and isolated from the fermented media, and the respective design and scale-up of a pilot-plant of the biopharmaceutical purification will be developed in the last stage. Aiming a future industrial application, the ATPS scale-up will be developed for batch and continuous processes. Summing up, it will be expected the development and study the industrial applicability, of new methodologies, capable of to promote the purification of diverse biopharmaceutical compounds with pharmaceutical, industrial and economical high-value, using more sustainable and inert processes, and exhibiting higher rates of selectivity and purification yields. (AU)

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Scientific publications (41)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MUSSAGY, CASSAMO U.; PEREIRA, JORGE F. B.; DUFOSSE, LAURENT; RAGHAVAN, VIJAYA; SANTOS-EBINUMA, VALERIA C.; PESSOA JR, ADALBERTO. Advances and trends in biotechnological production of natural astaxanthin by Phaffia rhodozyma yeast. CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, AUG 2021. Web of Science Citations: 0.
KURNIK, ISABELLE S.; D'ANGELO, NATALIA A.; MAZZOLA, PRISCILA G.; CHORILLI, MARLUS; KAMEI, DANIEL T.; PEREIRA, JORGE F. B.; VICENTE, ANTONIO A.; LOPES, ANDRE M. Polymeric micelles using cholinium-based ionic liquids for the encapsulation and release of hydrophobic drug molecules. BIOMATERIALS SCIENCE, v. 9, n. 6, p. 2183-2196, MAR 21 2021. Web of Science Citations: 0.
PEREZ-SANCHEZ, GERMAN; SCHAEFFER, NICOLAS; LOPES, ANDRE M.; PEREIRA, JORGE F. B.; COUTINHO, JOAO A. P. Using coarse-grained molecular dynamics to understand the effect of ionic liquids on the aggregation of Pluronic copolymer solutions. Physical Chemistry Chemical Physics, v. 23, n. 10, p. 5824-5833, MAR 14 2021. Web of Science Citations: 1.
DE OLIVEIRA, FERNANDA; HIRAI, PATRICIA RIE; SIMAS TEIXEIRA, MARIA FRANCISCA; PEREIRA, JORGE F. B.; SANTOS-EBINUMA, VALERIA C. Talaromyces amestolkiae cell disruption and colorant extraction using imidazolium-based ionic liquids. Separation and Purification Technology, v. 257, FEB 15 2021. Web of Science Citations: 1.
SOARES, BRUNA P.; SANTOS, JOAO H. P. M.; MARTINS, MARGARIDA; ALMEIDA, MAFALDA R.; SANTOS, V, NATHALIA; FREIRE, MARA G.; SANTOS-EBINUMA, VALERIA C.; COUTINHO, JOAO A. P.; PEREIRA, JORGE F. B.; VENTURA, SONIA P. M. Purification of green fluorescent protein using fast centrifugal partition chromatography. Separation and Purification Technology, v. 257, FEB 15 2021. Web of Science Citations: 0.
MUSSAGY, CASSAMO USSEMANE; CARIZIA GUIMARAES, ANA ALICE; FERREIRA ROCHA, LARA VICENTE; WINTERBURN, JAMES; SANTOS-EBINUMA, VALERIA DE CARVALHO; BRANDAO PEREIRA, JORGE FERNANDO. Improvement of carotenoids production from Rhodotorula glutinis CCT-2186. Biochemical Engineering Journal, v. 165, JAN 15 2021. Web of Science Citations: 5.
TORRES-ACOSTA, MARIO A.; DOS SANTOS, V, NATHALIA; VENTURA, SONIA P. M.; COUTINHO, JOAO A. P.; RITO-PALOMARES, MARCO; PEREIRA, JORGE F. B. Economic analysis of the production and recovery of green fluorescent protein using ATPS-based bioprocesses. Separation and Purification Technology, v. 254, JAN 1 2021. Web of Science Citations: 0.
MUSSAGY, CASSAMO U.; SANTOS-EBINUMA, VALERIA C.; KURNIA, KIKI A.; DIAS, V, ANA C. R.; CARVALHO, PEDRO; COUTINHO, JOAO A. P.; PEREIRA, JORGE F. B. Integrative platform for the selective recovery of intracellular carotenoids and lipids from Rhodotorula glutinis CCT-2186 yeast using mixtures of bio-based solvents. GREEN CHEMISTRY, v. 22, n. 23, p. 8478-8494, DEC 7 2020. Web of Science Citations: 0.
DOS SANTOS, NATHALIA VIEIRA; SAPONI, CAROLINA FALASCHI; RYAN, TIMOTHY M.; PRIMO, FERNANDO L.; GREAVES, TAMAR L.; PEREIRA, JORGE F. B. Reversible and irreversible fluorescence activity of the Enhanced Green Fluorescent Protein in pH: Insights for the development of pH-biosensors. International Journal of Biological Macromolecules, v. 164, p. 3474-3484, DEC 1 2020. Web of Science Citations: 0.
KURNIK, ISABELLE S.; MUSSAGY, CASSAMO U.; PEREIRA, JORGE F. B.; LOPES, ANDRE M. Amphiphilic copolymer aqueous solutions with cholinium ionic liquids as adjuvants: New insights into determination of binodal curves and phase-separation mechanisms. JOURNAL OF MOLECULAR LIQUIDS, v. 318, NOV 15 2020. Web of Science Citations: 0.
KURNIK, ISABELLE S.; NORONHA, MARIANA A.; CAMARA, MAYRA C. C.; MAZZOLA, PRISCILA G.; VICENTE, ANTONIO A.; PEREIRA, JORGE F. B.; LOPES, ANDRE M. Separation and purification of curcumin using novel aqueous two-phase micellar systems composed of amphiphilic copolymer and cholinium ionic liquids. Separation and Purification Technology, v. 250, NOV 1 2020. Web of Science Citations: 0.
MUSSAGY, CASSAMO U.; TABANEZ, NAIARA L.; FARIAS, FABIANE O.; KURNIA, KIKI A.; MAFRA, MARCOS R.; PEREIRA, JORGE F. B. Determination, characterization and modeling of aqueous biphasic systems composed of propylammonium-based ionic liquids and phosphate salts. Chemical Physics Letters, v. 754, SEP 2020. Web of Science Citations: 0.
BARROS, HELENA D. F. Q.; MAXIMO, GUILHERME J.; CAZARIN, CINTHIA B. B.; PEREIRA, JORGE F. B.; MAROSTICA JUNIOR, MARIO R. Subacute toxicity assessment of biobased ionic liquids in rats. Food Research International, v. 134, AUG 2020. Web of Science Citations: 0.
MAGRI, AGNES; PIMENTA, MARCELA V.; SANTOS, JOAO H. P. M.; COUTINHO, JOAO A. P.; VENTURA, SONIA P. M.; MONTEIRO, GISELE; RANGEL-YAGUI, CARLOTA O.; PEREIRA, JORGE F. B. Controlling the l-asparaginase extraction and purification by the appropriate selection of polymer/salt-based aqueous biphasic systems. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 95, n. 4, p. 1016-1027, APR 2020. Web of Science Citations: 3.
ALVES CAMELO, LIDIA CRISTINA; DIAS SANTOS, GABRIELA DE SOUZA; DE SOUZA, RANYERE LUCENA; FARIA SOARES, CLEIDE MARA; BRANDAO PEREIRA, JORGE FERNANDO; LIMA, ALVARO SILVA. Protic ionic liquids as constituent of aqueous two-phase system based on acetonitrile: Synthesis, phase diagrams and genipin pre-purification. Fluid Phase Equilibria, v. 507, MAR 1 2020. Web of Science Citations: 0.
PEREIRA, JORGE F. B.; FREIRE, MARA G.; COUTINHO, JOAO A. P. Aqueous two-phase systems: Towards novel and more disruptive applications. Fluid Phase Equilibria, v. 505, FEB 1 2020. Web of Science Citations: 2.
FARIAS, FABIANE OLIVEIRA; PEREIRA, JORGE F. B.; COUTINHO, JOAO A. P.; IGARASHI-MAFRA, LUCIANA; MAFRA, MARCOS R. Understanding the role of the hydrogen bond donor of the deep eutectic solvents in the formation of the aqueous biphasic systems. Fluid Phase Equilibria, v. 503, JAN 1 2020. Web of Science Citations: 1.
MAGRI, AGNES; PECORARI, THAINA; PEREIRA, MATHEUS M.; CILLI, EDUARDO M.; GREAVES, TAMAR L.; PEREIRA, JORGE F. B. Enhancing the Biocatalytic Activity of L-Asparaginase Using Aqueous Solutions of Cholinium-Based Ionic Liquids. ACS SUSTAINABLE CHEMISTRY & ENGINEERING, v. 7, n. 24, p. 19720-19731, DEC 16 2019. Web of Science Citations: 0.
MAGRI, AGNES; PIMENTA, MARCELA V.; SANTOS, JOAO H. P. M.; COUTINHO, JOAO A. P.; VENTURA, SONIA P. M.; MONTEIRO, GISELE; RANGEL-YAGUI, CARLOTA O.; PEREIRA, JORGE F. B. Controlling the l-asparaginase extraction and purification by the appropriate selection of polymer/salt-based aqueous biphasic systems. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 95, n. 4 DEC 2019. Web of Science Citations: 0.
MUSSAGY, CASSAMO U.; SANTOS-EBINUMA, VALERIA C.; GONZALEZ-MIQUEL, MARIA; COUTINHO, JOAO A. P.; PEREIRA, JORGE F. B. Protic Ionic Liquids as Cell-Disrupting Agents for the Recovery of Intracellular Carotenoids from Yeast Rhodotorula glutinis CCT-2186. ACS SUSTAINABLE CHEMISTRY & ENGINEERING, v. 7, n. 19, p. 16765-16776, OCT 7 2019. Web of Science Citations: 0.
NASCIMENTO, PALOMA A. M.; PICHELI, FLAVIO P.; LOPES, ANDRE M.; PEREIRA, JORGE F. B.; SANTOS-EBINUMA, VALERIA C. Effects of cholinium-based ionic liquids on Aspergillus niger lipase: Stabilizers or inhibitors. BIOTECHNOLOGY PROGRESS, v. 35, n. 5 SEP-OCT 2019. Web of Science Citations: 1.
FERRARI, FELIPE AUGUSTO; BRANDAO PEREIRA, JORGE FERNANDO; WITKAMP, GEERT-JAN; SOARES FORTE, MARCUS BRUNO. Which Variables Matter for Process Design and Scale-Up? A Study of Sugar Cane Straw Pretreatment Using Low-Cost and Easily Synthesizable Ionic Liquids. ACS SUSTAINABLE CHEMISTRY & ENGINEERING, v. 7, n. 15, p. 12779-12788, AUG 5 2019. Web of Science Citations: 0.
DOS SANTOS, NATHALIA VIEIRA; SAPONI, CAROLINA FALASCHI; GREAVES, TAMAR LOUISE; BRANDAO PEREIRA, JORGE FERNANDO. Revealing a new fluorescence peak of the enhanced green fluorescent protein using three-dimensional fluorescence spectroscopy. RSC ADVANCES, v. 9, n. 40, p. 22853-22858, AUG 1 2019. Web of Science Citations: 0.
LOPES, CAMILA; DOS SANTOS, NATHALIA VIEIRA; DUPONT, JANA; PEDROLLI, DANIELLE BISCARO; VALENTINI, SANDRO ROBERTO; SANTOS-EBINUMA, VALERIA DE CARVALHO; BRANDAO PEREIRA, JORGE FERNANDO. Improving the cost effectiveness of enhanced green fluorescent protein production using recombinant Escherichia coli BL21 (DE3): Decreasing the expression inducer concentration. Biotechnology and Applied Biochemistry, v. 66, n. 4, p. 527-536, JUL 2019. Web of Science Citations: 0.
MARTINS NASCIMENTO, PALOMA ANDRADE; BRANDAO PEREIRA, JORGE FERNANDO; SANTOS-EBINUMA, VALERIA DE CARVALHO. Insights into the effect of imidazolium-based ionic liquids on chemical structure and hydrolytic activity of microbial lipase. Bioprocess and Biosystems Engineering, v. 42, n. 7, p. 1235-1246, JUL 2019. Web of Science Citations: 1.
RODRIGUES, K. C. S.; COSTA, C. L. L.; BADINO, A. C.; PEDROLLI, D. B.; PEREIRA, J. F. B.; CERRI, M. O. Application of Acid and Cold Stresses to Enhance the Production of Clavulanic Acid by Streptomyces clavuligerus. Applied Biochemistry and Biotechnology, v. 188, n. 3, p. 706-719, JUL 2019. Web of Science Citations: 1.
MUSSAGY, CASSAMO USSEMANE; WINTERBURN, JAMES; SANTOS-EBINUMA, VALERIA CARVALHO; BRANDAO PEREIRA, JORGE FERNANDO. Production and extraction of carotenoids produced by microorganisms. Applied Microbiology and Biotechnology, v. 103, n. 3, p. 1095-1114, FEB 2019. Web of Science Citations: 8.
LOPES, ANDRE MORENI; DUTRA MOLINO, JOAO VITOR; DOS SANTOS-EBINUMA, VALERIA CARVALHO; PESSOA, JR., ADALBERTO; VALENTINI, SANDRO ROBERTO; BRANDAO PEREIRA, JORGE FERNANDO. Effect of electrolytes as adjuvants in GFP and LPS partitioning on aqueous two-phase systems: 1. Polymer-polymer systems. Separation and Purification Technology, v. 206, p. 39-49, NOV 29 2018. Web of Science Citations: 4.
MAGRI, AGNES; SOLER, MATHEUS F.; LOPES, ANDRE M.; CILLI, EDUARDO M.; BARBER, PATRICK S.; PESSOA, JR., ADALBERTO; PEREIRA, JORGE F. B. A critical analysis of L-asparaginase activity quantification methods-colorimetric methods versus high-performance liquid chromatography. ANALYTICAL AND BIOANALYTICAL CHEMISTRY, v. 410, n. 27, p. 6985-6990, NOV 2018. Web of Science Citations: 4.
TORRES-ACOSTA, MARIO A.; PEREIRA, JORGE F. B.; FREIRE, MARA G.; AGUILAR-YANEZ, JOSE M.; COUTINHO, JOAO A. P.; TITCHENER-HOOKER, NIGEL J.; RITO-PALOMARES, MARCO. Economic evaluation of the primary recovery of tetracycline with traditional and novel aqueous two-phase systems. Separation and Purification Technology, v. 203, p. 178-184, SEP 12 2018. Web of Science Citations: 4.
DOS SANTOS, NATHALIA V.; MARTINS, MARGARIDA; SANTOS-EBINUMA, VALERIA C.; VENTURA, SONIA P. M.; COUTINHO, JOAO A. P.; VALENTINI, SANDRO R.; PEREIRA, JORGE F. B. Aqueous Biphasic Systems Composed of Cholinium Chloride and Polymers as Effective Platforms for the Purification of Recombinant Green Fluorescent Protein. ACS SUSTAINABLE CHEMISTRY & ENGINEERING, v. 6, n. 7, p. 9383-9393, JUL 2018. Web of Science Citations: 6.
DOS SANTOS, NATHALIA VIEIRA; SANTOS-EBINUMA, VALERIA DE CARVALHO; PESSOA JUNIOR, ADALBERTO; BRANDAO PEREIRA, JORGE FERNANDO. Liquid-liquid extraction of biopharmaceuticals from fermented broth: trends and future prospects. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 93, n. 7, SI, p. 1845-1863, JUL 2018. Web of Science Citations: 9.
MARTINS, MARGARIDA; OOI, CHIEN WEI; NEVES, MARCIA C.; PEREIRA, JORGE F. B.; COUTINHO, JOAO A. P.; VENTURA, SONIA P. M. Extraction of recombinant proteins from Escherichia coli by cell disruption with aqueous solutions of surface-active compounds. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 93, n. 7, SI, p. 1864-1870, JUL 2018. Web of Science Citations: 4.
HIJO, ARIEL A. C. TOLEDO; MAXIMO, GUILHERME J.; CUNHA, ROSIANE L.; FONSECA, FELIPE H. S.; CARDOSO, LISANDRO P.; PEREIRA, JORGE F. B.; COSTA, MARIANA C.; BATISTA, EDUARDO A. C.; MEIRELLES, ANTONIO J. A. Phase equilibrium and physical properties of biobased ionic liquid mixtures. Physical Chemistry Chemical Physics, v. 20, n. 9, p. 6469-6479, MAR 7 2018. Web of Science Citations: 5.
PANAS, PAWEL; LOPES, CAMILA; CERRI, MARCEL O.; VENTURA, SONIA P. M.; SANTOS-EBINUMA, VALERIA C.; PEREIRA, JORGE F. B. Purification of clavulanic acid produced by Streptomyces clavuligerus via submerged fermentation using polyethylene glycol/cholinium chloride aqueous two-phase systems. Fluid Phase Equilibria, v. 450, p. 42-50, OCT 25 2017. Web of Science Citations: 7.
PEREIRA, JORGE F. B.; BARBER, PATRICK S.; KELLEY, STEVEN P.; BERTON, PAULA; ROGERS, ROBIN D. Double salt ionic liquids based on 1-ethyl-3-methylimidazolium acetate and hydroxyl-functionalized ammonium acetates: strong effects of weak interactions. Physical Chemistry Chemical Physics, v. 19, n. 39, p. 26934-26943, OCT 21 2017. Web of Science Citations: 8.
SILVA, FRANCISCA A. E; PEREIRA, JORGE F. B.; KURNIA, KIKI A.; VENTURA, SONIA P. M.; SILVA, ARTUR M. S.; ROGERS, ROBIN D.; COUTINHO, JOAO A. P.; FREIRE, MARA G. Temperature dependency of aqueous biphasic systems: an alternative approach for exploring the differences between Coulombic-dominated salts and ionic liquids. CHEMICAL COMMUNICATIONS, v. 53, n. 53, p. 7298-7301, JUL 7 2017. Web of Science Citations: 6.
TOLEDO HIJO, ARIEL A. C.; MAXIMO, GUILHERME J.; COSTA, MARIANA C.; CUNHA, ROSIANE L.; PEREIRA, JORGE F. B.; KURNIA, KIKI A.; BATISTA, EDUARDO A. C.; MEIRELLES, ANTONIO J. A. Phase Behavior and Physical Properties of New Biobased Ionic Liquid Crystals. Journal of Physical Chemistry B, v. 121, n. 14, p. 3177-3189, APR 13 2017. Web of Science Citations: 14.
CLAUDIO, ANA FILIPA M.; PEREIRA, JORGE F. B.; MCCRARY, PARKER D.; FREIRE, MARA G.; COUTINHO, JOAO A. P.; ROGERS, ROBIN D. A critical assessment of the mechanisms governing the formation of aqueous biphasic systems composed of protic ionic liquids and polyethylene glycol. Physical Chemistry Chemical Physics, v. 18, n. 43, p. 30009-30019, NOV 21 2016. Web of Science Citations: 6.
NEVES, CATARINA M. S. S.; SHAHRIARI, SHAHLA; LEMUS, JESUS; PEREIRA, JORGE F. B.; FREIRE, MARA G.; COUTINHO, JOAO A. P. Aqueous biphasic systems composed of ionic liquids and polypropylene glycol: insights into their liquid-liquid demixing mechanisms. Physical Chemistry Chemical Physics, v. 18, n. 30, p. 20571-20582, AUG 14 2016. Web of Science Citations: 17.
PEREIRA, JORGE F. B.; KURNIA, KIKI A.; FREIRE, MARA G.; COUTINHO, JOAO A. P.; ROGERS, ROBIN D. Controlling the Formation of Ionic-Liquid-based Aqueous Biphasic Systems by Changing the Hydrogen-Bonding Ability of Polyethylene Glycol End Groups. ChemPhysChem, v. 16, n. 10, p. 2219-2225, JUL 20 2015. Web of Science Citations: 14.

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