Therapeutic l-asparaginase: upstream, downstream and beyond

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dc.contributor.authorLopes, André Moreni
dc.contributor.authorOliveira-Nascimento, Laura de
dc.contributor.authorRibeiro, Artur
dc.contributor.authorTairum, Carlos Abrunhosa [UNESP]
dc.contributor.authorBreyer, Carlos Alexandre [UNESP]
dc.contributor.authorOliveira, Marcos Antonio de [UNESP]
dc.contributor.authorMonteiro, Gisele
dc.contributor.authorSouza-Motta, Cristina Maria de
dc.contributor.authorMagalhães, Pérola de Oliveira
dc.contributor.authorAvendaño, Jorge Gonzalo Farías
dc.contributor.authorCavaco-Paulo, Artur Manuel
dc.contributor.authorMazzola, Priscila Gava
dc.contributor.authorRangel-Yagui, Carlota de Oliveira
dc.contributor.authorSette, Lara Durães [UNESP]
dc.contributor.authorConverti, Attilio
dc.contributor.authorPessoa, Adalberto
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversity of Minho
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de Pernambuco (UFPE)
dc.contributor.institutionUniversity of Brasilia–UnB
dc.contributor.institutionUniversity of La Frontera
dc.contributor.institutionUniversity of Genoa
dc.date.accessioned2018-12-11T16:59:49Z
dc.date.available2018-12-11T16:59:49Z
dc.date.issued2017-01-02
dc.description.abstractl-asparaginase (l-asparagine amino hydrolase, E.C.3.5.1.1) is an enzyme clinically accepted as an antitumor agent to treat acute lymphoblastic leukemia and lymphosarcoma. It catalyzes l-asparagine (Asn) hydrolysis to l-aspartate and ammonia, and Asn effective depletion results in cytotoxicity to leukemic cells. Microbial l-asparaginase (ASNase) production has attracted considerable attention owing to its cost effectiveness and eco-friendliness. The focus of this review is to provide a thorough review on microbial ASNase production, with special emphasis to microbial producers, conditions of enzyme production, protein engineering, downstream processes, biochemical characteristics, enzyme stability, bioavailability, toxicity and allergy potential. Some issues are also highlighted that will have to be addressed to achieve better therapeutic results and less side effects of ASNase use in cancer treatment: (a) search for new sources of this enzyme to increase its availability as a drug; (b) production of new ASNases with improved pharmacodynamics, pharmacokinetics and toxicological profiles, and (c) improvement of ASNase production by recombinant microorganisms. In this regard, rational protein engineering, directed mutagenesis, metabolic flux analysis and optimization of purification protocols are expected to play a paramount role in the near future.en
dc.description.affiliationDepartment of Biochemical and Pharmaceutical Technology School of Pharmaceutical Sciences University of São Paulo
dc.description.affiliationDepartment of Biochemistry and Tissue Biology Institute of Biology State University of Campinas–UNICAMP
dc.description.affiliationCentre of Biological Engineering (CEB) School of Engineering University of Minho
dc.description.affiliationBiosciences Institute Coastal Campus São Paulo State University–UNESP
dc.description.affiliationDepartment of Mycology Federal University of Pernambuco
dc.description.affiliationDepartment of Pharmacy School of Health Sciences University of Brasilia–UnB
dc.description.affiliationDepartment of Chemical Engineering Faculty of Engineering and Science University of La Frontera
dc.description.affiliationFaculty of Pharmaceutical Sciences University of Campinas–UNICAMP
dc.description.affiliationDepartment of Biochemistry and Microbiology Institute of Biosciences São Paulo State University–UNESP
dc.description.affiliationDepartment of Civil Chemical and Environmental Engineering University of Genoa
dc.description.affiliationUnespBiosciences Institute Coastal Campus São Paulo State University–UNESP
dc.description.affiliationUnespDepartment of Biochemistry and Microbiology Institute of Biosciences São Paulo State University–UNESP
dc.format.extent82-99
dc.identifierhttp://dx.doi.org/10.3109/07388551.2015.1120705
dc.identifier.citationCritical Reviews in Biotechnology, v. 37, n. 1, p. 82-99, 2017.
dc.identifier.doi10.3109/07388551.2015.1120705
dc.identifier.file2-s2.0-84951292119.pdf
dc.identifier.issn1549-7801
dc.identifier.issn0738-8551
dc.identifier.lattes5969653098289575
dc.identifier.scopus2-s2.0-84951292119
dc.identifier.urihttp://hdl.handle.net/11449/172344
dc.language.isoeng
dc.relation.ispartofCritical Reviews in Biotechnology
dc.relation.ispartofsjr1,243
dc.relation.ispartofsjr1,243
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectAcute lymphoblastic leukemia
dc.subjectantineoplastic activity
dc.subjectbiopharmaceutical
dc.subjectl-asparaginase
dc.subjectmicrobial l-asparaginase production
dc.titleTherapeutic l-asparaginase: upstream, downstream and beyonden
dc.typeResenha
unesp.author.lattes5969653098289575

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