Advanced search
Start date
Betweenand

Optimization and economic feasibility study of recombinant L-asparaginase production process for pharmaceutical application

Grant number: 17/21819-9
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2018
Status:Discontinued
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Adalberto Pessoa Junior
Grantee:Larissa Pereira Brumano
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical, AP.TEM
Associated scholarship(s):19/03981-9 - Evaluation of the physiological changes during L-asparaginase production and extraction and economic viability of the process for pharmaceutical application, BE.EP.PD

Abstract

L-asparginase (ASNase) is an important medicine used in the treatment of lymphatic system oncological diseases, mainly acute lymphoblastic leukemia. In Brazil ASNase is provided by the government, however the country does not own the production technology yet, being dependent on international companies. ASNase's national shortage crisis has been discussed since 2011, but has recently worsened due to questions about the procurement process and the quality of ASNase provided. Currently, the acquisition of this biopharmaceutical is subject of discussion among society, physicians, academics and government, highlighting the urgency of national autonomy in ASNase production. This project is part of the FAPESP Thematic Project 2013/08617-7 and aims to contribute to the development of an industrially viable ASNase production process for pharmaceutical application. Therefore, recombinant strain E. coli BL21(DE3) able to overexpress protease resistant ASNase will be used. This strain was developed in the context of the Thematic Project. Optimization of nutritional and operational parameters of fermentation processes will be studied, as well as high cell density culture using fed-batch process and the best purification strategy in order to obtain high ASNase productivity. In addition, evaluation of alterations in intracellular pH and membrane permeability during the production process (aiming to understand enzyme exportation mechanism and the influence of the culture conditions on cellular physiology) and the technical-economic process viability, using experimental results of cultivation optimization and enzyme purification will be performed. These two last steps will be carried out in collaboration with Prof. Dr. Solange Mussatto at the Technical University of Denmark. The results obtained in this project will be essential for the establishment and feasibility of the process, which will contribute to the development and implementation of a new technology, generating important knowledge in the area, considering the relevance and the actuality of the subject.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BRUMANO, LARISSA PEREIRA; SANTOS DA SILVA, FRANCISCO VITOR; COSTA-SILVA, TALES ALEXANDRE; APOLINARIO, ALEXSANDRA CONCEICAO; PICADO MADALENA SANTOS, JOAO HENRIQUE; KLEINGESINDS, EDUARDO KREBS; MONTEIRO, GISELE; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; BENYAHIA, BRAHIM; PESSOA JUNIOR, ADALBERTO. Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 6, JAN 10 2019. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Distribution map of accesses to this page
Click here to view the access summary to this page.