Abstract
The treatment of acute lymphoblastic leukemia is challenging due to side effects, efficacy of the available drugs, and costs. Utilization of L-asparaginase as a therapeutic agent is essential to increase survival of patients. However, costs are elevated and the bacterial forms of the enzyme cause reactions that result in its inhibition by the immune system. Therapeutics alternatives may be searched among eukaryote producers, like fungi. Twelve strains of filamentous fungi were evaluated regarding expression of L-asparaginase activity. The profile of nitrogen assimilation and radial growth were determined for strains which showed higher production ratios. Three media were formulated after selection of the carbon source and carbon/nitrogen ratio that better induced L-asparaginase expression by Penicillium sp. and Fusarium sp. The enzyme activity produced in liquid media reached 8.3 U min.-1 mL-1 (Penicillium sp. T6.2) and 11.4 U min.-1 mL-1 (Fusarium sp.) after 72 hours of cultivation in Bacelar-1 medium. These data show that good producers can be found among fungi, and adjustment of productive processes may offer an alternative to implement eukaryote L-asparaginase production.
Highlights
The enzyme L-asparaginase (EC 3.5.1.1)catalyzes the hydrolysis of L-asparagine in Laspartate and ammonia (Figure 1) (ExPASy, 2016)
Fungi have long been known as good enzyme producers. Their absorptive mode of nutrition requires an efficient secretion of enzymes to decompose nutrients in the extracellular medium, so that the presence of an inducer substrate usually activates production of the enzyme required for its utilization
T6.1, Aspergillus tubingensis AN1257, Aspergillus niger N402 (ATCC® 64974TM) were screened to search L-asparaginase producers. Among these 12 fungal strains cultivated in CzapekDox/Bromothymol blue (BTB) agar, three strains - Penicillium sp
Summary
The enzyme L-asparaginase (EC 3.5.1.1)catalyzes the hydrolysis of L-asparagine in Laspartate and ammonia (Figure 1) (ExPASy, 2016). When administered as a therapeutic agent, its catalytic activity results in depletion of L-asparagine in the bloodstream and in apoptosis of leukemic cells, which are incapable of producing this aminoacid (Ando et al, 2005). Leukemic cells depend on absorption of L-asparagine from the blood, while healthy cells produce it internally. Based on this action, the enzyme is used to increase event freesurvival in children with acute lymphoblastic leukemia (ALL), and to treat several other malignancies of the lymphoid system (Zuo, Zhang, Jiang, & Wanmeng, 2015). The pharmacological use of L-asparaginase started after Broome (1963) who verified that the enzyme was the anti-leukemic bioactive compound in guinea pig serum.
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