Evaluation of the physiological changes during L-asparaginase production and extraction and economic viability of the process for pharmaceutical application

• Grant number: 19/03981-9
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: September 09, 2019
• End date: September 08, 2020
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Adalberto Pessoa Junior
• Grantee: Larissa Pereira Brumano
• Supervisor: Solange Ines Mussatto Dragone
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Technical University of Denmark (DTU), Denmark
• Associated to the scholarship: 17/21819-9 - Optimization and economic feasibility study of recombinant L-asparaginase production process for pharmaceutical application, BP.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. Due to the crisis of shortages and controversies regarding the quality of the imported drug, research is urgently needed to make production feasible in the country. The search for a high-quality and technical-economically viable ASNase production process is a strategy of great economic, social and public health importance in Brazil. During the first step of the postdoctoral project, studies of culture medium composition and operating parameters aiming at a higher productivity of the process were conducted. However, for the downstream step, the yield of the ASNase extraction from periplasmic space proved to be a process bottleneck. At the project approved (FAPESP 2017/21819-9), a research internship abroad (BEPE) was planned, which is essential for the achievement of the proposed objectives and will contribute substantially for strengthening research through the partnership with Dr. Solange Mussatto´s research group (Technical University of Denmark - Novo Nordisk Foundation Center for Biosustainability/DTU Biosustain). This group has a solid experience in bioprocess and technical-economic studies, as well as advanced structure and international leadership in the field. Thus, taking advantage of support and expertise of Dr. Mussatto´s research group, analyses of physiological changes by the study of membrane permeability and intracellular pH (pHi) at cultivation conditions and during enzyme extraction will be carried at DTU, as well as the technical-economic analysis of the bioprocess, based in the experimental results obtained so far and in literature. The understanding of the culture conditions´ influence on membrane permeability and pHi is important in order to better comprehend the bacterial production and exportation of the enzyme and the use of this techniques can contribute to overcome the challenge of enzyme extraction yield. The other objective of the BEPE is to advance in the technical-economic analysis that is fundamental in the search for a viable industrial process. Besides obtaining excellence results, the internationalization of research, strengthening of productive partnerships and improvement of techniques that can be implemented in Brazil are also important results expected with the execution of this proposal.

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)

MOGUEL, IGNACIO S.; YAMAKAWA, CELINA K.; BRUMANO, LARISSA P.; PESSOA, ADALBERTO; MUSSATTO, SOLANGE I.. Selection and Optimization of Medium Components for the Efficient Production of L-Asparaginase by Leucosporidium scottii L115-A Psychrotolerant Yeast. FERMENTATION-BASEL, v. 8, n. 8, p. 16-pg., 2022-08-01. (13/08617-7, 19/03981-9)