L-asparaginase production review: bioprocess design and biochemical characteristics

resumo

In the past decades, the production of biopharmaceuticals has gained high interest due to its great sensitivity, specificity, and lower risk of negative effects to patients. Biopharmaceuticals are mostly therapeutic recombinant proteins produced through biotechnological processes. In this context, L-asparaginase (L-asparagine amidohydrolase, L-ASNase (E.C. 3.5.1.1)) is a therapeutic enzyme that has been abundantly studied by researchers due to its antineoplastic properties. As a biopharmaceutical, L-ASNase has been used in the treatment of acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), and other lymphoid malignancies, in combination with other drugs. Besides its application as a biopharmaceutical, this enzyme is widely used in food processing industries as an acrylamide mitigation agent and as a biosensor for the detection of L-asparagine in physiological fluids at nano-levels. The great demand for L-ASNase is supplied by recombinant enzymes from Escherichia coli and Erwinia chrysanthemi. However, production processes are associated to low yields and proteins associated to immunogenicity problems, which leads to the search for a better enzyme source. Considering the L-ASNase pharmacological and food importance, this review provides an overview of the current biotechnological developments in L-ASNase production and biochemical characterization aiming to improve the knowledge about its production.

palavras-chave

EXTRACELLULAR L-ASPARAGINASE; RECOMBINANT L-ASPARAGINASE; I L-ASPARAGINASE; CHRYSANTHEMI L-ASPARAGINASE; SOLID-STATE FERMENTATION; ESCHERICHIA-COLI; BACILLUS-SUBTILIS; SACCHAROMYCES-CEREVISIAE; SUBMERGED FERMENTATION; ENHANCED PRODUCTION

categoria

Biotechnology & Applied Microbiology

autores

Castro, D; Marques, ASC; Almeida, MR; de Paiva, GB; Bento, HBS; Pedrolli, DB; Freire, MG; Tavares, APM; Santos-Ebinuma, VC

nossos autores

agradecimentos

This work was funded by the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES; by FEDER, through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI); by national funds (OE), through FCT/MCTES (POCI-01-0145-FEDER-031268); by the FCT Investigator Programme and Exploratory Project (IF/01634/2015) with financing from the European Social Fund and the Human Potential Operational Programme; by FAPESP (2018/06908-8, 2020/15513-7); and by the CAPES (Coordination of Superior Level Staff Improvement, Brazil), finance code 001.

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