abstract
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.
keywords
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
subject category
Biotechnology & Applied Microbiology
authors
Castro, D; Marques, ASC; Almeida, MR; de Paiva, GB; Bento, HBS; Pedrolli, DB; Freire, MG; Tavares, APM; Santos-Ebinuma, VC
our authors
Ana Mafalda Rodrigues Almeida Rocha
Researcher
Ana Paula Mora Tavares
Assistant Researcher
Mara Guadalupe Freire Martins
Coordinating ResearcherProjects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Projeto de Investigação Exploratória: Ana Paula Tavares (IF Ana Paula Tavares)
acknowledgements
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.