Production of L-asparaginase using genetically modified microorganism

• Grant number: 19/01757-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2019
• End date: March 31, 2020
• Field of knowledge: Engineering - Chemical Engineering - Chemical Process Industries
• Agreement: Fundação para a Ciência e a Tecnologia (FCT)
• Principal Investigator: Valéria de Carvalho Santos Ebinuma
• Grantee: Juliano Sales Mendes
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 18/06908-8 - Development of sustainable nanomaterials for the purification of antileukemic drugs, AP.R

Abstract

In the area of health, this project has a strong component of new biotechnologies and advanced solutions forthe production of biopharmaceuticals to be used as therapeutic agents in various types of cancer, specifically inleukemia. L-asparaginase (E.C.3.5.1.1) (ASNase) is the enzyme that catalyzes the hydrolysis reaction of theamino acid side chain of the amino acid L-asparagine, releasing aspartic acid and ammonia, being widely used asanti-neoplastic agent. This enzyme can be produced by a number of microorganisms, however, there is a need fornew producing sources with higher yields and lower adverse effects. Thus, the objective of this project is toevaluate the production of L-asparaginase by recombinant microorganism through new process and productdevelopment solutions, namely in the optimization of the production process and in the use of differentmicroorganisms with greater production capacity. Initially, screening of ASNase production will be done withdifferent heterologous microbial expression systems on a rotary shaker. Afterwards, a rotating shaker study willbe performed using different sources and concentrations of nitrogen, glucose concentration (carbon source), initialpH and culture temperature. The development of new L-asparaginase production lines will lead to a moreeffective, more effective therapeutic with reduced side effects.