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Production and purification of recombinant proteins of pharmaceutical interest

Grant number: 14/50237-0
Support type:Regular Research Grants
Duration: August 01, 2014 - March 31, 2016
Field of knowledge:Biological Sciences - Microbiology
Cooperation agreement: Universidad de la Frontera
Principal Investigator:Adalberto Pessoa Junior
Grantee:Adalberto Pessoa Junior
Principal investigator abroad: Jorge Farias Avendaño
Institution abroad: Universidad de La Frontera (UFRO), Chile
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

Abstract

There is a strong global tendency to find alternative ways to produce pharmaceutical active principies from biotechnology processo In this scenario, Brazil shows a small expression in both research and production. Worsening the situation, international suppliers of biopharmaceuticals to Brazil are losing interest in the market and discontinuing production, especially those related to onco-hematologic treatment. In this context, this project proposes the union of different scientific and technological skills to achieve a viable industrial process to biotechnologically produce L-Asparaginase, a biopharmaceutical broadly used in the treatment of leukemia. This project will approach two main areas: optimization of endogenous and heterologous enzyme production, with bioprospecting groups of fungi from diverse biomes; and the protein rational engineering using L-Asparaginase from S. cerevisiae as scaffold for comparative studies with the bacterial isoforms currently employed in the therapy. Furthermore, crystallographic structures will be determined to guide the site-directed mutations and random mutations produced by protein synthetic evolution will be evaluated. To improve stability, bioavailability, toxicity and allergenic aspects, many nanotechnology approaches, such as pegylation and nanoencapsulation in polimerosomes, will be investigated. As a result, we expect this project can bring a national biopharmaceutical to the market. Both groups are expecting academic gains in new knowledge according to the expertise of the researchers involved in this proposal. For example, the USP group will receive researchers with experience in enzyme characterization, and metabolic engineering of enzymes, as well as the UFRO group will receive experts in fermentation technology, nanotechnology, liquid liquid extraction of proteins, and molecular biology of yeasts. (AU)