Review on up and downstream processing of L-asparaginase.

Abstract

L-asparaginase (asparagine amidohydrolase) contributes to 40% of the total enzyme demands worldwide and is one-third of the global requirement as an anti-cancerous drug in treating acute lymphocytic leukemia (ALL), a type of leukemia. This protein breaks down L-asparagine into aspartic acid and ammonia those involved in ALL, rely on for growth and survival. Both non-recombinant and recombinant L-asparaginase can be produced by bacteria when a suitable substrate and method (solid-state fermentation (SSF) or submerged fermentation (SmF) which are techniques to grow microorganisms under controlled conditions), is provided. Between both L-asparaginase's isozymes, asparaginase type II displays higher specific action against L-asparagine and precisely shows antitumor activity. The applied methods in purification of L-asparaginase in the frame of three phases of protein purification strategy known as CIPP (including capture, intermediate purification, and polishing phase) are discussed in this review. Depending on whether the production of the enzyme is intracellular or extracellular, various steps in each phase, like removal of insoluble material, extraction, concentration, and purification, must followed. In this review, authors summarize the upstream processes in L-asparaginase production and the various applied chromatographic and non-chromatographic methods in each step of CIPP, in downstream processes.