Journal
BIOTECHNOLOGY ADVANCES
Volume 24, Issue 5, Pages 514-528Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biotechadv.2006.05.002
Keywords
urokinase synthesis and regulation; urokinase production; tissue plasminogen activator; process integration
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Urokinase, a serine protease, catalyzes the conversion of plasminogen to plasmin, which is responsible for dissolution of clots in blood vessels. It is an important drug for treatment of thromboembolic disease. Production of urokinase by mammalian cell culture has the following important steps: synthesis, regulation and secretion. Production and accumulation of this product in a bioreactor is a real challenge for biochemical engineers. Considerable information at molecular level needs to be understood for production of urokinase in order to correlate different parameters, which in turn can maximize the productivity. This information will be highlighted in this review. Moreover, urokinase production is a product-inhibited process. Therefore, in situ urokinase separation strategy is required to operate a bioreactor at its maximum urokinase formation rate. Integrated urokinase production and isolation processes developed recently will also be discussed briefly in this review. (c) 2006 Elsevier Inc. All rights reserved.
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