Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical

• Grant number: 13/08617-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: July 01, 2014
• End date: December 31, 2019
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Adalberto Pessoa Junior
• Grantee: Adalberto Pessoa Junior
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Principal investigators: Gisele Monteiro ; Marcos Antonio de Oliveira
• Associated researchers: Attilio Converti ; Carlota de Oliveira Rangel Yagui ; Cristina Maria de Souza Motta ; João Carlos Monteiro de Carvalho ; Jorge Gonzalo Farias Avendano ; Lara Durães Sette ; Pérola de Oliveira e Magalhães ; Priscila Gava Mazzola ; Sandra Helena Poliselli Farsky
• Associated research grant(s): 15/02482-8 - Multi-user equipment related to grant 201308617-7 - HPLC coupled with mass spectrometry, AP.EMU
• Associated scholarship(s): 18/25994-2 - Development of novel platforms for PEGylation of proteins with therapeutic potential using microfluidics, BP.PD; 18/24926-3 - L-Asparaginase production by recombinant Escherichia coli in high cell density cultivation for a pharmaceutical application, BP.DR; 18/25133-7 - Production and Characterization of Lyposomes and Polymersomes for Encapsulation of L-asparaginase., BP.IC; + associated scholarships 17/20384-9 - Development of downstream process of humanized L-Asparaginase and its characterization, BP.DR; 18/15041-8 - Expression of L-asparaginase from Erwinia chrysanthemi in Cell-free Protein Synthesis Technology, BP.MS; 17/25272-4 - Asparaginase 1 from Saccharomyces cerevisiae: Investigation of the functional and structural effects of the N-terminal domain, BP.IC; 18/03734-9 - Implementation of Quality by Design to the Development of the Production Process of the Chemotherapeutical Enzyme L- Asparaginase, BP.PD; 17/21819-9 - Optimization and economic feasibility study of recombinant L-asparaginase production process for pharmaceutical application, BP.PD; 17/27230-7 - Heterologous expression and functional and structural characterization of asparaginase RmASP1 of Rhodotorula mucilaginosa, BP.IC; 17/25065-9 - Production of L-asparaginase by Pichia pastoris in fed-batch bioreactors, BP.DD; 17/12458-2 - Biochemical characteristics and antitumor activity of the recombinant protein L-asparaginase I small, BP.IC; 16/25896-5 - Biochemical characterization and cytotoxic evaluation of mutant isoforms of L-Asparaginase II from Dickeya chrysanthemi (Erwinia chrysanthemi), BP.DR; 16/19245-1 - Evaluation of bacterial strains to L-Asparaginase super expression: An antileukemic enzime from Escherichia Coli, BP.IC; 16/15787-4 - Cloning of L-Asparaginase from Escherichia coli in a Pichia pastoris strain with humanized glysosylation, BP.IC; 16/01869-9 - Therapeutic l-asp for LLA purification employing alternative bioproces, BP.MS; 16/16221-4 - DEVELOPMENT OF POLYMERSOMES PERMEABLE TO L-ASPARAGINE FOR ENCAPSULATION OF L-ASPARAGINASE, BP.PD; 16/09138-3 - Engineering of the signal secretory portion of asparaginase from Saccharomyces cerevisiae for extracellular biopharmaceutical production., BP.IC; 15/24463-5 - Characterization of L-asparaginase of erwinia chysanthemi improved by synthetic evolution of proteins and optimization of production conditions, BP.DD; 15/20866-8 - Saccharomyces cerevisiae L-asparaginase 1:Rational modifications aiming the modulation of kinectic chatacteristics over different substrates., BP.IC; 15/04349-3 - Screening of inhibitory molecules for human Peroxiredoxin II , seeking treatment for Acute Lymphoid Leukemia (ALL), BP.MS; 14/22039-9 - Functional and structural characterization and rational modification of ASPaseM: A new pharmaceutical for the acute lymphoblastic leukemia treatment?, BP.DD; 14/10456-4 - DEVELOPMENT AND CHARACTERIZATION OF POLY(ETHYLENE GLYCOL) METHYL ETHER-BLOCK-POLY(D,L-LACTIDE) (PEG-PLA) POLYMERSOMES FOR THE RELEASE OF RECOMBINANT L-ASPARAGINASE, BP.DR - associated scholarships

Abstract

There is a strong global tendency to find alternative ways to produce pharmaceutical active principles from biotechnology process. In this scenario, Brazil shows a small expression in both research and production. Worsening the situation, international suppliers of biopharmaceuticals to Brazil are losing interest in the market and discontinuing production, especially those related to onco-hematologic treatment. In this context, this project proposes the union of different scientific and technological skills to achieve a viable industrial process to biotechnologically produce L-asparaginase, a biopharmaceutical broadly used in the treatment of leukemia. This project will approach two main areas: optimization of endogenous and heterologous enzyme production, with bioprospecting groups of fungi from diverse biomes; and the protein rational engineering using L-asparaginase from Saccharomyces cerevisiae as scaffold for comparative studies with the bacterial isoforms currently employed in the therapy. Furthermore, crystallographic structures will be determined to guide the site-directed mutations, and random mutations produced by protein synthetic evolution will be evaluated. To improve stability, bioavailability, toxicity and allergenic aspects, many nanotechnology approaches, such as pegylation and nanoencapsulation in polimersomes, will be investigated. As a result, we expect this project can bring a national biopharmaceutical to the market. (AU)

Scientific publications

(66)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

LOUISE LACALENDOLA TUNDISI; DIEGO DE FREITAS COÊLHO; ALESSANDRA VALÉRIA DE SOUSA FARIA; ADALBERTO PESSOA JUNIOR; ELIAS BASILE TAMBOURGI; LAURA DE OLIVEIRA NASCIMENTO; EDGAR SILVEIRA; PRISCILA GAVA MAZZOLA. Two-Step Purification of L-Asparaginase from Acrylaway® L. Brazilian Journal of Pharmaceutical Sciences, v. 58, 2022-08-08. (13/08617-7, 16/01869-9)

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. (14/16424-7, 14/01580-3, 14/19793-3, 13/08617-7, 16/07529-5)

SANTOS, JOAO H. P. M.; FLORES-SANTOS, JUAN C.; MENEGUETTI, GIOVANNA P.; RANGEL-YAGUI, CARLOTA O.; COUTINHO, JOAO A. P.; VITOLO, MICHELE; VENTURA, SONIA P. M.; PESSOA, JR., ADALBERTO. In situ purification of periplasmatic L-asparaginase by aqueous two phase systems with ionic liquids (ILs) as adjuvants. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 93, n. 7, SI, p. 1871-1880, JUL 2018. (13/08617-7)

DE MOURA, WERNER ALFINITO FEIO; SCHULTZ, LEONARDO; BREYER, CARLOS ALEXANDRE; DE OLIVEIRA, ANA LAURA PIRES; TAIRUM, CARLOS ABRUNHOSA; FERNANDES, GABRIELLA COSTA; TOYAMA, MARCOS HIKARI; PESSOA-JR, ADALBERTO; MONTEIRO, GISELE; DE OLIVEIRA, MARCOS ANTONIO. Functional and structural evaluation of the antileukaemic enzymel-asparaginase II expressed at low temperature by differentEscherichia colistrains. Biotechnology Letters, JUL 2020. (13/08617-7, 17/19942-7, 17/25272-4, 19/04054-4, 14/22039-9, 16/19245-1, 17/20291-0, 11/13500-6)

ALEXSANDRA CONCEIÇÃO APOLINÁRIO; JULIANA DE ALMEIDA PACHIONI-VASCONCELOS; ADALBERTO PESSOA JR.; CARLOTA DE OLIVEIRA RANGEL-YAGUI. POLIMEROSSOMOS VERSUS LIPOSSOMOS: A EVOLUÇÃO DA “BALA MÁGICA”. Química Nova, v. 40, n. 7, p. 810-817, 2017-08-00. (14/10456-4, 13/08617-7)

BIASOTO, HENRIQUE P.; HEBEDA, CRISTINA B.; FARSKY, SANDRA H. P.; PESSOA, ADALBERTO; COSTA-SILVA, TALES A.; MONTEIRO, GISELE. Extracellular expression of Saccharomyces cerevisiae's L-asparaginase II in Pichia pastoris results in novel enzyme with better parameters. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. N/A, p. 12-pg., 2022-08-16. (13/08617-7, 18/15104-0, 16/09138-3, 15/07749-2)

KLEINGESINDS, EDUARDO KREBS; PARIZOTTO, LETICIA DE ALMEIDA; EFFER, BRIAN; MONTEIRO, GISELE; LONG, PAUL F.; ARROYO-BERDUGO, YOANA; BEHRENDS, VOLKER; ESPOSITO, MARIA TERESA; CALLE, YOLANDA; PESSOA-JR, ADALBERTO. Downstream process and evaluation of the concomitant impact of a recombinant glycosylated L-asparaginase on leukemic cancer cells and the bone marrow tumor microenvironment. Process Biochemistry, v. 131, p. 11-pg., 2023-06-09. (19/06919-2, 13/08617-7, 15/07749-2, 18/03734-9, 17/25065-9, 17/20384-9, 18/15104-0)

HERRERA BELEN, LISANDRA; BELTRAN LISSABET, JORGE F.; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; MONTEIRO, GISELE; PESSOA, ADALBERTO; FARIAS, JORGE G.. Immunogenicity assessment of fungal L-asparaginases: an in silico approach. SN APPLIED SCIENCES, v. 2, n. 2, FEB 2020. (13/08617-7)

WLODARCZYK, SAMARINA R.; CUSTODIO, DEBORA; PESSOA JR, ADALBERTO; MONTEIRO, GISELE. Influence and effect of osmolytes in biopharmaceutical formulations. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v. 131, p. 92-98, OCT 2018. (15/24463-5, 13/08617-7, 13/24024-6, 15/07749-2)

TORRES-OBREQUE, KARIN; MENEGUETTI, GIOVANNA PASTORE; CUSTODIO, DEBORA; MONTEIRO, GISELE; PESSOA-JUNIOR, ADALBERTO; DE OLIVEIRA RANGEL-YAGUI, CARLOTA. Production of a novel N-terminal PEGylated crisantaspase. Biotechnology and Applied Biochemistry, v. 66, n. 3, p. 281-289, MAY-JUN 2019. (16/22065-5, 13/08617-7)

DANIELA CAMARGO FURUYA; SILGIA APARECIDA DA COSTA; RODRIGO CARDOSO DE OLIVEIRA; HUMBERTO GOMES FERRAZ; ADALBERTO PESSOA JUNIOR; SIRLENE MARIA DA COSTA. Fibers Obtained from Alginate, Chitosan and Hybrid Used in the Development of Scaffolds. MATERIALS RESEARCH-IBERO-AMERICAN JOURNAL OF MATERIALS, v. 20, n. 2, p. 377-386, 2017-01-23. (13/08617-7)

SANTOS, JOAO H. P. M.; COSTA, IRIS M.; MOLINO, JOAO V. D.; LEITE, MARIANA S. M.; PIMENTA, MARCELA V.; COUTINHO, JOAO A. P.; PESSOA, JR., ADALBERTO; VENTURA, SONIA P. M.; LOPES, ANDRE M.; MONTEIRO, GISELE. Heterologous expression and purification of active L-asparaginase I of Saccharomyces cerevisiae in Escherichia coli host. BIOTECHNOLOGY PROGRESS, v. 33, n. 2, p. 416-424, MAR-APR 2017. (15/07749-2, 13/08617-7)

COSTA-SILVA, T. A.; CAMACHO-CORDOVA, D. I.; AGAMEZ-MONTALVO, G. S.; PARIZOTTO, L. A.; SANCHEZ-MOGUEL, I.; PESSOA-, JR., A.. Optimization of culture conditions and bench-scale production of anticancer enzyme L-asparaginase by submerged fermentation from Aspergillus terreus CCT 7693. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. 49, n. 1, p. 95-104, JAN 2 2019. (13/08617-7, 13/19584-2)

EFFER, BRIAN; LIMA, GUILHERME MEIRA; CABARCA, SINDY; PESSOA, ADALBERTO; FARIAS, JORGE G.; MONTEIRO, GISELE. L-Asparaginase from E. chrysanthemi expressed in glycoswitch: effect of His-Tag fusion on the extracellular expression. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. 49, n. 7, APR 2019. (17/20384-9, 16/25896-5, 15/07749-2, 13/08617-7, 16/15787-4)

MEDEIROS DE BRITO, ANNA EMMANUELA; PESSOA, JR., ADALBERTO; CONVERTI, ATTILIO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; DA SILVA, JOSE ALEXSANDRO; APOLINARIO, ALEXSANDRA CONCEICAO. Poly (lactic-co-glycolic acid) nanospheres allow for high L-asparaginase encapsulation yield and activity. Materials Science & Engineering C-Materials for Biological Applications, v. 98, p. 524-534, MAY 2019. (13/08617-7, 14/10456-4, 17/08123-5)

LOPES, ANDRE MORENI; RIBEIRO, ARTUR; DE OLIVEIRA, MARCOS ANTONIO; DE SOUZA-MOTTA, CRISTINA MARIA; MAGALHAES, PEROLA DE OLIVEIRA; FARIAS AVENDANO, JORGE GONZALO; MAZZOLA, PRISCILA GAVA; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Therapeutic l-asparaginase: upstream, downstream and beyond. CRITICAL REVIEWS IN BIOTECHNOLOGY, v. 37, n. 1, p. 82-99, 2017. (13/08617-7, 13/19486-0)

LIMA, GUILHERME M.; ATRAZHEV, ALEXEY; SARKAR, SUSMITA; SOJITRA, MIRAT; REDDY, REVATHI; TORRES-OBREQUE, KARIN; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; MACAULEY, MATTHEW S.; MONTEIRO, GISELE; DERDA, RATMIR. DNA-Encoded Multivalent Display of Chemically Modified Protein Tetramers on Phage: Synthesis and in Vivo Applications. ACS Chemical Biology, DEC 2021. (13/08617-7, 16/22065-5, 18/15041-8, 19/09354-6, 18/15104-0)

CARDOSO, SAMUEL L.; DE FREITAS, MARCELA M.; DE SOUZA, PAULA M.; HOMEM-DE-MELLO, MAURICIO; SILVEIRA, DAMARIS; FONSECA-BAZZO, YRIS MARIA; FILHO, EDIVALDO X.; JUNIOR, ADALBERTO P.; MAGALHAES, PEROLA O.. Optimization of aqueous two-phase micellar system for partial purification of L-asparaginase from Penicillium sp. grown in wheat bran as agro-industrial residue. Brazilian Journal of Microbiology, v. 51, n. 3, MAY 2020. (13/08617-7)

SANTOS-EBINUMA, VALERIA CARVALHO; LOPES, ANDRE MORENI; PESSOA, JR., ADALBERTO; SIMAS TEIXEIRA, MARIA FRANCISCA. Extraction of natural red colorants from the fermented broth of Penicillium purpurogenum using aqueous two-phase polymer systems. BIOTECHNOLOGY PROGRESS, v. 31, n. 5, p. 1295-1304, SEP-OCT 2015. (13/08617-7)

FLORES-SANTOS, JUAN CARLOS; MOGUEL, IGNACIO S.; MONTEIRO, GISELE; PESSOA, ADALBERTO; VITOLO, MICHELE. Improvement in extracellular secretion of recombinant l-asparaginase II by Escherichia coli BL21 (DE3) using glycine and n-dodecane. Brazilian Journal of Microbiology, v. 52, n. 3, p. 1247-1255, SEP 2021. (13/08617-7)

SANCHEZ-MOGUEL, IGNACIO; COSTA-SILVA, TALES A.; PILLACA-PULLO, OMAR S.; FLORES-SANTOS, JUAN CARLOS; BARROS FREIRE, ROMINNE KARLA; CARRETERO, GUSTAVO; BUENO, JULIA DA LUZ; CAMACHO-CORDOVA, DAVID I.; SANTOS, JOAO H. P. M.; SETTE, LARA DURAES; et al. Antarctic yeasts as a source of L-asparaginase: Characterization of a glutaminase-activity free L-asparaginase from psychrotolerant yeast Leucosporidium scottii L115. Process Biochemistry, v. 129, p. 12-pg., 2023-03-21. (19/23620-0, 13/19584-2, 13/08617-7)

SANTOS, JOAO H. P. M.; MENDONCA, CARLOS M. N.; SILVA, AMANDA R. P.; OLIVEIRA, RICARDO P. S.; PESSOA JR, ADALBERTO; COUTINHO, JOAO A. P.; VENTURA, SONIA P. M.; RANGEL-YAGUI, CARLOTA O.. An integrated process combining the reaction and purification of PEGylated proteins. GREEN CHEMISTRY, v. 21, n. 23, p. 6407-6418, DEC 7 2019. (16/22065-5, 13/08617-7, 18/25994-2)

COSTA, IRIS MUNHOZ; SCHULTZ, LEONARDO; BIANCHI PEDRA, BEATRIZ DE ARAUJO; MOREIRA LEITE, MARIANA SILVA; FARSKY, SANDRA H. P.; DE OLIVEIRA, MARCOS ANTONIO; PESSOA, ADALBERTO; MONTEIRO, GISELE. Recombinant L-asparaginase 1 from Saccharomyces cerevisiae: an allosteric enzyme with antineoplastic activity. SCIENTIFIC REPORTS, v. 6, NOV 8 2016. (13/16685-2, 13/08617-7, 15/07749-2)

GUIMARAES, MARINA DE SOUZA; MUSO CACHUMBA, JORGE JAVIER; BUENO, CECILIA ZORZI; TORRES-OBREQUE, KARIN MARIANA; RUIZ LARA, GRACE VERONICA; MONTEIRO, GISELE; SOUZA BARBOSA, LEANDRO RAMOS; PESSOA JR, ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Peg-Grafted Liposomes for L-Asparaginase Encapsulation. PHARMACEUTICS, v. 14, n. 9, p. 18-pg., 2022-09-01. (18/15104-0, 13/08617-7, 15/15822-1, 14/10456-4)

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. (13/08617-7, 18/15104-0, 14/16424-7, 18/25994-2, 14/19793-3, 15/07749-2)

MOGUEL, IGNACIO S.; YAMAKAWA, CELINA K.; BRUMANO, LARISSA P.; PESSOA, ADALBERTO; MUSSATTO, SOLANGE I.. Selection and Optimization of Medium Components for the Efficient Production of L-Asparaginase by Leucosporidium scottii L115-A Psychrotolerant Yeast. FERMENTATION-BASEL, v. 8, n. 8, p. 16-pg., 2022-08-01. (13/08617-7, 19/03981-9)

TUNDISI, LOUISE LACALENDOLA; COELHO, DIEGO DE FREITAS; DE SOUSA FARIA, ALESSANDRA VALERIA; PESSOA JUNIOR, ADALBERTO; TAMBOURGI, ELIAS BASILE; NASCIMENTO, LAURA DE OLIVEIRA; SILVEIRA, EDGAR; MAZZOLA, PRISCILA GAVA. Two-Step Purification of L-Asparaginase from Acrylaway((R)) L. Brazilian Journal of Pharmaceutical Sciences, v. 58, p. 13-pg., 2022-01-01. (16/01869-9, 13/08617-7)

EFFER, BRIAN; KLEINGESINDS, EDUARDO KREBS; LIMA, GUILHERME MEIRA; COSTA, IRIS MUNHOZ; SANCHEZ-MOGUEL, IGNACIO; PESSOA, ADALBERTO; SANTIAGO, VERONICA FEIJOLI; PALMISANO, GIUSEPPE; FARIAS, JORGE G.; MONTEIRO, GISELE. Glycosylation of Erwinase results in active protein less recognized by antibodies. Biochemical Engineering Journal, v. 163, p. 11-pg., 2020-11-15. (13/08617-7, 15/07749-2, 17/20384-9, 18/15104-0, 16/15787-4, 16/25896-5)

SCHULTZ, L.; MONTEIRO, G.; PESSOA-, A., JR.; DE OLIVEIRA, M. A.. A new L-asparaginase as a promising biodrug to acute lymphoblastic leukemia treatment. Annals of Oncology, v. 27, p. 2-pg., 2016-12-01. (13/08617-7)

FERREIRA, ADAMO; FUGANHOLI, NICOLA SGRIGNOLI; SILVA, MARINA S. R.; TORRES-OBREQUE, KARIN MARIANA; G. FERREIRA, RAFAEL; PESSOA JR, ADALBERTO; AZZONI, ADRIANO RODRIGUES. Industrial Production of PEGylated L-asparaginase: Process Design and Techno-economic Assessment Through Simulation. Applied Biochemistry and Biotechnology, v. N/A, p. 21-pg., 2025-10-11. (20/06982-3, 13/08617-7, 19/23620-0)

APOLINARIO, ALEXSANDRA CONCEICAO; FERRARO, RAFAEL BERTELLI; DE OLIVEIRA, CAMILA AREIAS; PESSOA, ADALBERTO, JR.; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using "Off-the-Shelf" Materials: a Study on L-Asparaginase. AAPS PHARMSCITECH, v. 20, n. 6, p. 12-pg., 2019-08-01. (14/10456-4, 16/03887-4, 13/08617-7, 17/03811-0)

LIMA, GUILHERME MEIRA; EFFER, BRIAN; BIASOTO, HENRIQUE PELLIN; FEIJOLI, VERONICA; PESSOA, ADALBERTO; PALMISANO, GIUSEPPE; MONTEIRO, GISELE. Glycosylation of L-asparaginase from E. coli through yeast expression and site-directed mutagenesis. Biochemical Engineering Journal, v. 156, p. 11-pg., 2020-04-15. (14/06863-3, 16/15787-4, 18/15549-1, 18/18257-1, 15/07749-2, 13/08617-7)

APOLINARIO, ALEXSANDRA CONCEICAO; FERRARO, RAFAEL BERTELLI; DE OLIVEIRA, CAMILA AREIAS; PESSOA, JR., ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using ``Off-the-Shelf{''} Materials: a Study on L-Asparaginase. AAPS PHARMSCITECH, v. 20, n. 6, AUG 2019. (17/03811-0, 13/08617-7, 16/03887-4, 14/10456-4)

DA SILVA, LEONARDO SCHULTZ; DOONAN, LIAM B.; PESSOA, JR., ADALBERTO; DE OLIVEIRA, MARCOS ANTONIO; LONG, PAUL F.. Structural and functional diversity of asparaginases: Overview and recommendations for a revised nomenclature. Biotechnology and Applied Biochemistry, MAR 2021. (18/04685-1, 13/08617-7, 14/22039-9, 17/19942-7)

LIMA, GUILHERME M.; MENEZES, MILENE C.; COSTA, IRIS M.; SERRANO, SOLANGE M. T.; MONTEIRO, GISELE. Development of a cell-free protein synthesis protocol to rapidly screen L-asparaginase proteoforms by enzymatic activity. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, JUN 2021. (13/08617-7, 18/15041-8, 16/25896-5, 13/07467-1, 18/15104-0)

FLORES-SANTOS, JUAN CARLOS; MOGUEL, IGNACIO S.; MONTEIRO, GISELE; PESSOA, ADALBERTO; VITOLO, MICHELE. Improvement in extracellular secretion of recombinant l-asparaginase II by Escherichia coli BL21 (DE3) using glycine and n-dodecane. Brazilian Journal of Microbiology, JUN 2021. (13/08617-7)

DA ROCHA, W. R. V.; COSTA-SILVA, T. A.; AGAMEZ-MONTALVO, G. S.; FEITOSA, V. A.; MACHADO, S. E. F.; DE SOUZA LIMA, G. M.; PESSOA-, JR., A.; ALVES, H. S.. Screening and optimizing fermentation production of l-asparaginase by Aspergillus terreus strain S-18 isolated from the Brazilian Caatinga Biome. Journal of Applied Microbiology, v. 126, n. 5, p. 1426-1437, MAY 2019. (13/19584-2, 13/08617-7)

SANTOS, JOAO H. P. M.; BRUMANO, LARISSA P.; PESSOA, JR., ADALBERTO; RANGEL-YAGUI, CARLOTA O.. Tailoring Protein PEGylation Reaction: An Undergraduate Laboratory Experiment. Journal of Chemical Education, v. 97, n. 5, p. 1443-1447, MAY 12 2020. (17/21819-9, 16/22065-5, 13/08617-7, 18/25994-2)

JOZALA, ANGELA FAUSTINO; DE LENCASTRE-NOVAES, LETICIA CELIA; LOPES, ANDRE MORENI; SANTOS-EBINUMA, VALERIA DE CARVALHO; MAZZOLA, PRISCILA GAVA; PESSOA-, JR., ADALBERTO; GROTTO, DENISE; GERENUTTI, MARLI; CHAUD, MARCO VINICIUS. Bacterial nanocellulose production and application: a 10-year overview. Applied Microbiology and Biotechnology, v. 100, n. 5, p. 2063-2072, MAR 2016. (09/14897-7, 13/08617-7)

APOLINARIO, ALEXSANDRA CONCEICAO; MAGON, MONIKA S.; PESSOA JR, ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Challenges for the Self-Assembly of Poly(Ethylene Glycol)-Poly(Lactic Acid) (PEG-PLA) into Polymersomes: Beyond the Theoretical Paradigms. NANOMATERIALS, v. 8, n. 6, JUN 2018. (13/08617-7, 14/10456-4)

MENEGUETTI, GIOVANNA PASTORE; PICADO MADALENA SANTOS, JOAO HENRIQUE; TORRES OBREQUE, KARIN MARIANA; VAZ BARBOSA, CHRISTIANO MARCELLO; MONTEIRO, GISELE; POLISELLI FARSKY, SANDRA HELENA; DE OLIVEIRA, ADRIANO MARIM; ANGELI, CLAUDIA BLANES; PALMISANO, GIUSEPPE; MARQUES VENTURA, SONIA PATRICIA; et al. Novel site-specific PEGylated L-asparaginase. PLoS One, v. 14, n. 2, FEB 12 2019. (16/22065-5, 13/08617-7)

RODRIGUES, DAVID; PILLACA-PULLO, OMAR; TORRES-OBREQUE, KARIN; FLORES-SANTOS, JUAN; SANCHEZ-MOGUEL, IGNACIO; PIMENTA, V, MARCELA; BASI, TAJINDAR; CONVERTI, ATTILIO; LOPES, ANDRE M.; MONTEIRO, GISELE; et al. Fed-Batch Production of Saccharomyces cerevisiae L-Asparaginase II by Recombinant Pichia pastoris MUTs Strain. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 7, FEB 8 2019. (13/08617-7, 17/10789-1)

PACHIONI-VASCONCELOS, JULIANA DE ALMEIDA; LOPES, ANDRE MORENI; APOLINARIO, ALEXSANDRA CONCEICAO; VALENZUELA-OSES, JOHANNA KARINA; RIBEIRO COSTA, JULIANA SOUZA; NASCIMENTO, LAURA DE OLIVEIRA; PESSOA, JR., ADALBERTO; SOUZA BARBOSA, LEANDRO RAMOS; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Nanostructures for protein drug delivery. BIOMATERIALS SCIENCE, v. 4, n. 2, p. 205-218, 2016. (14/01983-0, 13/16588-7, 13/08617-7, 14/10456-4)

TUNDISI, LOUISE L.; COELHO, DIEGO F.; ZANCHETTA, BEATRIZ; MORIEL, PATRICIA; PESSOA, JR., ADALBERTO; TAMBOURGI, ELIAS B.; SILVEIRA, EDGAR; MAZZOLA, PRISCILA G.. L-Asparaginase Purification. SEPARATION AND PURIFICATION REVIEWS, v. 46, n. 1, p. 35-43, 2016. (13/08617-7)

COSTA-SILVA, TALES A.; FLORES-SANTOS, JUAN CARLOS; FREIRE, ROMINNE K. B.; VITOLO, MICHELE; PESSOA-, JR., ADALBERTO. Microbial cell disruption methods for efficient release of enzyme L-asparaginase. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. 48, n. 8, p. 707-717, 2018. (13/08617-7, 13/19584-2)

BONUGLI-SANTOS, RAFAELLA C.; DOS SANTOS VASCONCELOS, MARIA R.; PASSARINI, MICHEL R. Z.; VIEIRA, GABRIELA A. L.; LOPES, VIVIANE C. P.; MAINARDI, PEDRO H.; DOS SANTOS, JULIANA A.; DUARTE, LIDIA DE AZEVEDO; OTERO, IGOR V. R.; DA SILVA YOSHIDA, ALINE M.; et al. Marine-derived fungi: diversity of enzymes and biotechnological applications. FRONTIERS IN MICROBIOLOGY, v. 6, APR 10 2015. (13/00286-1, 08/06720-7, 13/12505-0, 13/08617-7, 11/18769-3, 09/18399-1, 13/19486-0, 12/12622-3)

DANIELA CAMARGO FURUYA; SILGIA APARECIDA DA COSTA; RODRIGO CARDOSO DE OLIVEIRA; HUMBERTO GOMES FERRAZ; ADALBERTO PESSOA JUNIOR; SIRLENE MARIA DA COSTA. Fibers Obtained from Alginate, Chitosan and Hybrid Used in the Development of Scaffolds. MATERIALS RESEARCH-IBERO-AMERICAN JOURNAL OF MATERIALS, n. ahead, p. 0-0, 2017. (13/08617-7)

LIMA, GUILHERME M.; ATRAZHEV, ALEXEY; SARKAR, SUSMITA; SOJITRA, MIRAT; REDDY, REVATHI; TORRES-OBREQUE, KARIN; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; MACAULEY, MATTHEW S.; MONTEIRO, GISELE; DERDA, RATMIR. DNA-Encoded Multivalent Display of Chemically Modified Protein Tetramers on Phage: Synthesis and in Vivo Applications. ACS Chemical Biology, v. 17, n. 11, p. 12-pg., 2022-11-18. (19/09354-6, 16/22065-5, 18/15041-8, 13/08617-7, 18/15104-0)

BUENO, CECILIA Z.; APOLINARIO, ALEXSANDRA C.; DURO-CASTANO, AROA; POMA, ALESSANDRO; PESSOA, JR., ADALBERTO; RANGEL-YAGUI, CARLOTA O.; BATTAGLIA, GIUSEPPE. L-Asparaginase Encapsulation into Asymmetric Permeable Polymersomes. ACS MACRO LETTERS, v. 9, n. 10, p. 1471-1477, OCT 20 2020. (17/03811-0, 16/16221-4, 17/05272-0, 13/08617-7)

PILLACA-PULLO, OMAR; RODRIGUES, DAVID; SANCHEZ-MOGUEL, IGNACIO; LOPES, ANDRE; PIMENTA, MARCELA; BASI, TAJINDAR; FEITOSA, VALKER; IRIS ZAVALETA, AMPARO; MONTEIRO, GISELE; PESSOA JR, ADALBERTO; et al. Recombinantl-asparaginase production usingPichia pastoris(MUT(s)strain): establishment of conditions for growth and induction phases. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 1, AUG 2020. (13/08617-7, 17/10789-1)

FREIRE, ROMINNE KARLA BARROS; MENDONCA, CARLOS MIGUEL NOBREGA; FERRARO, RAFAEL BERTELLI; MOGUEL, IGNACIO SANCHEZ; TONSO, ALDO; LOURENCO, FELIPE REBELLO; SANTOS, JOAO HENRIQUE PICADO MADALENA; SETTE, LARA DURAES; PESSOA JUNIOR, ADALBERTO. Glutaminase-free L-asparaginase production byLeucosporidium muscorumisolated from Antarctic marine-sediment. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. 51, n. 3, SEP 2020. (18/25994-2, 13/08617-7)

COSTA-SILVA, T. A.; COSTA, I. M.; BIASOTO, H. P.; LIMA, G. M.; SILVA, C.; PESSOA, A.; MONTEIRO, G.. Critical overview of the main features and techniques used for the evaluation of the clinical applicability of L-asparaginase as a biopharmaceutical to treat blood cancer. BLOOD REVIEWS, v. 43, p. 17-pg., 2020-09-01. (18/15041-8, 13/08617-7, 16/25896-5, 15/07749-2)

DA SILVA, LEONARDO SCHULTZ; DOONAN, LIAM B.; PESSOA, ADALBERTO, JR.; DE OLIVEIRA, MARCOS ANTONIO; LONG, PAUL F.. Structural and functional diversity of asparaginases: Overview and recommendations for a revised nomenclature. Biotechnology and Applied Biochemistry, v. 69, n. 2, p. 11-pg., 2021-03-19. (18/04685-1, 13/08617-7, 17/19942-7, 14/22039-9)

BRUMANO, LARISSA PEREIRA; SANTOS DA SILVA, FRANCISCO VITOR; COSTA-SILVA, TALES ALEXANDRE; APOLINARIO, ALEXSANDRA CONCEICAO; PICADO MADALENA SANTOS, JOAO HENRIQUE; KLEINGESINDS, EDUARDO KREBS; MONTEIRO, GISELE; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; BENYAHIA, BRAHIM; PESSOA JUNIOR, ADALBERTO. Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 6, JAN 10 2019. (14/10456-4, 15/07749-2, 18/03734-9, 13/08617-7, 17/21819-9)

LIMA, GUILHERME MEIRA; EFFER, BRIAN; BIASOTO, HENRIQUE PELLIN; FEIJOLI, VERONICA; PESSOA, ADALBERTO; PALMISANO, GIUSEPPE; MONTEIRO, GISELE. Glycosylation of L-asparaginase from E. coli through yeast expression and site-directed mutagenesis. Biochemical Engineering Journal, v. 156, APR 15 2020. (15/07749-2, 13/08617-7, 14/06863-3, 18/18257-1, 18/15549-1, 16/15787-4)

PARIZOTTO, LETICIA DE ALMEIDA; KLEINGESINDS, EDUARDO KREBS; PEDROTTI DA ROSA, LUIZA MANFRINATO; EFFER, BRIAN; LIMA, GUILHERME MEIRA; HERKENHOFF, MARCOS EDGAR; LI, ZHAOPENG; RINAS, URSULA; MONTEIRO, GISELE; PESSOA, ADALBERTO; et al. Increased glycosylated L-asparaginase production through selection of Pichia pastoris platform and oxygen-methanol control in fed-batches. Biochemical Engineering Journal, v. 173, SEP 2021. (17/20384-9, 18/15041-8, 17/25065-9, 13/08617-7, 19/02583-0, 19/02657-3)

RODRIGUES, MARIANE A. D.; PIMENTA, MARCELA V.; COSTA, IRIS M.; ZENATTI, PRISCILA P.; MIGITA, NATACHA A.; YUNES, JOSE A.; RANGEL-YAGUI, CARLOTA O.; DE SA, MATHEUS M.; PESSOA, ADALBERTO; COSTA-SILVA, TALES A.; et al. Influence of lysosomal protease sensitivity in the immunogenicity of the antitumor biopharmaceutical asparaginase. Biochemical Pharmacology, v. 182, DEC 2020. (14/06863-3, 18/18257-1, 13/08617-7, 16/25896-5, 15/07749-2, 18/15104-0, 13/08139-8, 18/15549-1)

TORRES-OBREQUE, KARIN; KLEINGESINDS, EDUARDO KREBS; SANTOS, JOAO H. P. M.; CARRETERO, GUSTAVO; RABELO, JHENIFFER; CONVERTI, ATTILIO; MONTEIRO, GISELE; PESSOA JR, ADALBERTO; RANGEL-YAGUI, CARLOTA O.. PEGylation versus glycosylation: effect on the thermodynamics and thermostability of crisantaspase. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. N/A, p. 11-pg., 2023-09-11. (16/22065-5, 17/20384-9, 13/08617-7, 18/25994-2)

DE MOURA, WERNER ALFINITO FEIO; SCHULTZ, LEONARDO; BREYER, CARLOS ALEXANDRE; DE OLIVEIRA, ANA LAURA PIRES; TAIRUM, CARLOS ABRUNHOSA; FERNANDES, GABRIELLA COSTA; TOYAMA, MARCOS HIKARI; PESSOA-JR, ADALBERTO; MONTEIRO, GISELE; DE OLIVEIRA, MARCOS ANTONIO. Functional and structural evaluation of the antileukaemic enzymel-asparaginase II expressed at low temperature by differentEscherichia colistrains. Biotechnology Letters, v. 42, n. 11, p. 12-pg., 2020-07-07. (13/08617-7, 11/13500-6, 16/19245-1, 17/25272-4, 19/04054-4, 17/19942-7, 14/22039-9, 17/20291-0)

DA SILVA SANTOS, MARILIA GOMES; CAVALCANTI MACIEL, MARILIA DE HOLANDA; SOUSA, MINELLI ALBUQUERQUE; JULIAO BOMFIM, ALINE GLEYCE; PEREIRA BEZERRA, JADSON DIOGO; PESSOA JUNIOR, ADALBERTO; DE SOUZA-MOTTA, CRISTINA MARIA. Characterization and partial purification of L-asparaginase produced by endophytic fungi from cactus Cereus jamacaru. SYDOWIA, v. 74, p. 11-pg., 2022-01-01. (13/08617-7)

COSTA, IRIS MUNHOZ; MOURA, DEBORA CUSTODIO; LIMA, GUILHERME MEIRA; PESSOA, ADALBERTO; DOS SANTOS, CAMILA ORESCO; DE OLIVEIRA, MARCOS A.; MONTEIRO, GISELE. Engineered asparaginase from Erwinia chrysanthemi enhances asparagine hydrolase activity and diminishes enzyme immunoreactivity - a new promise to treat acute lymphoblastic leukemia. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 97, n. 1, OCT 2021. (16/25896-5, 15/07749-2, 18/15104-0, 13/08617-7)

LIMA, GUILHERME M.; MENEZES, MILENE C.; COSTA, IRIS M.; SERRANO, SOLANGE M. T.; MONTEIRO, GISELE. Development of a cell-free protein synthesis protocol to rapidly screen L-asparaginase proteoforms by enzymatic activity. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 9, p. 2659-2666, SEP 2021. (18/15041-8, 13/08617-7, 13/07467-1, 18/15104-0, 16/25896-5)

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, p. 19-pg., 2018-07-01. (14/16424-7, 14/01580-3, 16/07529-5, 13/08617-7, 14/19793-3)

PACHIONI-VASCONCELOS, JULIANA DE ALMEIDA; APOLINARIO, ALEXSANDRA CONCEICAO; LOPES, ANDRE MORENI; PESSOA, JR., ADALBERTO; BARBOSA, LEANDRO RAMOS SOUZA; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Compartmentalization of therapeutic proteins into semi-crystalline PEG-PCL polymersomes. SOFT MATERIALS, v. 19, n. 2, p. 222-230, APR 3 2021. (13/08617-7, 14/10456-4, 17/10789-1)

SANTOS, JOAO H. P. M.; FLORES-SANTOS, JUAN C.; MENEGUETTI, GIOVANNA P.; RANGEL-YAGUI, CARLOTA O.; COUTINHO, JOAO A. P.; VITOLO, MICHELE; VENTURA, SONIA P. M.; PESSOA, ADALBERTO, JR.. In situ purification of periplasmatic L-asparaginase by aqueous two phase systems with ionic liquids (ILs) as adjuvants. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 93, n. 7, p. 10-pg., 2018-07-01. (13/08617-7)

JAVIER, MUSO-CACHUMBA JORGE; GRACE, RUIZ-LARA; SANI, ALISON TATIANA MADRID; ZANIN, MARIA HELENA AMBROSIO; MONTEIRO, GISELE; LOURENCO, FELIPE REBELLO; PESSOA-JR, ADALBERTO; RANGEL-YAGUI, CARLOTA. Development of spray-dried formulation of glycosylated ASNase-loaded polymersomes based on quality by design approach. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 109, p. 13-pg., 2025-07-01. (13/08617-7, 18/15104-0)

Filed patent(s) as a result of this research project