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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Therapeutic l-asparaginase: upstream, downstream and beyond

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 3
Document type: Review article
Source: CRITICAL REVIEWS IN BIOTECHNOLOGY; v. 37, n. 1, p. 82-99, 2017.
Web of Science Citations: 23
Abstract

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)

FAPESP's process: 13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical
Grantee:Adalberto Pessoa Junior
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/19486-0 - Marine and Antarctic biotechnology: microbial enzymes and their applications
Grantee:Lara Durães Sette
Support Opportunities: Regular Research Grants