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

Grant number: 13/08617-7
Support type:Research Projects - Thematic Grants
Duration: July 01, 2014 - December 31, 2019
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Adalberto Pessoa Junior
Grantee:Adalberto Pessoa Junior
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Gisele Monteiro ; Marcos Antonio de Oliveira
Assoc. 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 grant(s):15/02482-8 - Multi-User Equipment related to grant 201308617-7 - HPLC coupled with mass spectrometry, AP.EMU
14/50237-0 - Production and purification of recombinant proteins of pharmaceutical interest, AP.R
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 bioprocess, 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)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Protein isolated from baker's yeast shows potential against leukemia cells 

Scientific publications (35)
(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)
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, SEP 2020. Web of Science Citations: 0.
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, SEP 2020. Web of Science Citations: 0.
PILLACA-PULLO, OMAR; RODRIGUES, DAVID; SANCHEZ-MOGUEL, IGNACIO; LOPES, ANDRE; PIMENTA, MARCELA; BASI, TAJINDAR; FEITOSA, VALKER; IRIS ZAVALETA, AMPARO; MONTEIRO, GISELE; PESSOA JR, ADALBERTO; VITOLO, MICHELE. Recombinantl-asparaginase production usingPichia pastoris(MUT(s)strain): establishment of conditions for growth and induction phases. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, AUG 2020. Web of Science Citations: 0.
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. Web of Science Citations: 0.
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. Web of Science Citations: 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. Web of Science Citations: 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, APR 15 2020. Web of Science Citations: 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. Web of Science Citations: 0.
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. 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.
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. Web of Science Citations: 0.
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. Web of Science Citations: 0.
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. Web of Science Citations: 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. Web of Science Citations: 1.
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. Web of Science Citations: 0.
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; PESSOA-JUNIOR, ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Novel site-specific PEGylated L-asparaginase. PLoS One, v. 14, n. 2 FEB 12 2019. Web of Science Citations: 4.
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; FONSECA, LUIS P.; PESSOA JR, ADALBERTO. 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. Web of Science Citations: 0.
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. Web of Science Citations: 3.
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. Web of Science Citations: 0.
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. Web of Science Citations: 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, SI, p. 1845-1863, JUL 2018. Web of Science Citations: 9.
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. Web of Science Citations: 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. Web of Science Citations: 4.
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. Web of Science Citations: 3.
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. Web of Science Citations: 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.
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. -, Ago. 2017.
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, Abr. 2017. Web of Science Citations: 8.
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. Web of Science Citations: 23.
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. Web of Science Citations: 13.
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. Web of Science Citations: 68.
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. Web of Science Citations: 25.
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. Web of Science Citations: 5.
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. Web of Science Citations: 5.
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.; FEITOSA, VALKER A.; PESSOA, JR., ADALBERTO; SETTE, LARA D. Marine-derived fungi: diversity of enzymes and biotechnological applications. FRONTIERS IN MICROBIOLOGY, v. 6, APR 10 2015. Web of Science Citations: 40.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Filed patent(s) as a result of this research project

MÉTODO DE OBTENÇÃO DE L-ASPARAGINASE RECOMBINANTE DE BAIXA MASSA MOLAR, L-ASPARAGINASE RECOMBINANTE E USO DA MESMA BR1020160247020 - Universidade de São Paulo (USP) ; Universidade Estadual Paulista (UNESP) . Marcos Antonio de Oliveira; Gisele Monteiro de Souza; Adalberto Pessoa Junior; Leonardo Schultz da Silva; Iris Munhoz Costa; Marcos Hiraki Toyama; Sandra Helena Poliselli Farsky - October 2016, 21