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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Therapeutic l-asparaginase: upstream, downstream and beyond

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Autor(es):
Lopes, Andre Moreni [1] ; Ribeiro, Artur ; de Oliveira, Marcos Antonio [2] ; de Souza-Motta, Cristina Maria ; Magalhaes, Perola de Oliveira ; Farias Avendano, Jorge Gonzalo ; Mazzola, Priscila Gava ; Rangel-Yagui, Carlota de Oliveira [13]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Sao Paulo State Univ UNESP, Biosci Inst, Coastal Campus, Sao Vicente, Brazil. de Souza-Motta, Cristina Maria, Univ Fed Pernambuco, Dept Mycol, Recife, PE, Brazil. Magalhaes, Perola de Oliveira, Univ Brasilia UnB, Sch Hlth Sci, Dept Pharm, Brasilia, DF, Br - Italy
[2] Cavaco-Paulo, Jr., Artur Manuel, Pessoa, Adalberto, Univ Sao Paulo, Sch Pharmaceut Sci, Dept Biochem \& Pharmaceut Technol, Sao Paulo, Brazil. de Oliveira-Nascimento, Laura, State Univ Campinas UNICAMP, Inst Biol, Dept Biochem \& Tissue Biol, Campinas, SP - Italy
[3] Sao Paulo State Univ UNESP, Biosci Inst, Coastal Campus, Sao Vicente, Brazil. de Souza-Motta, Cristina Maria, Univ Fed Pernambuco, Dept Mycol, Recife, PE, Brazil. Magalhaes, Perola de Oliveira, Univ Brasilia UnB, Sch Hlth Sci, Dept Pharm, Brasilia, DF, Brazil. Farias Avendano, Jorge Gonzalo, Univ La Frontera, Fac Sci & Engn, Dept Chem Engn, Temuco, Chile. Mazzola, Priscila Gava, Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP, Brazil. Sette, Lara Duraes, Sao Paulo State Univ UNESP, Inst Biosci, Dept Biochem & Microbiol, Rio Claro, Brazil. Converti, Attilio, Univ Genoa, Dept Civil Chem & Environm Engn, Genoa - Italy
Número total de Afiliações: 3
Tipo de documento: Artigo de Revisão
Fonte: CRITICAL REVIEWS IN BIOTECHNOLOGY; v. 37, n. 1, p. 82-99, 2017.
Citações Web of Science: 23
Resumo

l-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. (AU)

Processo FAPESP: 13/08617-7 - Produção de L-asparaginase extracelular: da bioprospecção à engenharia de um biofármaco antileucêmico
Beneficiário:Adalberto Pessoa Junior
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/19486-0 - Biotecnologia marinha e Antártica: enzimas microbianas e suas aplicações
Beneficiário:Lara Durães Sette
Modalidade de apoio: Auxílio à Pesquisa - Regular