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A plasminogen kringle domain 1 to 3, rK1-3, wasexpressed in Escherichia coli under the control of T7promoter. For the cost-effective production of rK1-3, theinduction process was analyzed and optimized. Inductioncharacteristics with lactose were analyzed in terms ofinduction time and inducer concentration in various cultureconditions including batch and high-cell-density fed-batchcultures. In the fed-batch culture, the induction around 6 hafter initiation of the DO-stat fed-batch culture resulted in thehighest expression level of rK1-3 among the induction pointsexamined. The highest demand of oxygen at this point wascrucial for the maximum expression level of rK1-3. As thelactose concentration increased, the expression level alsoincreased, though the expression level showed a plateauabove a concentration of 14 mM of lactose. Lactose acted lessspecifically than IPTG since most of it was hydrolyzed toglucose and galactose. However, using lactose, the cellgrowth and the maximum expression level of rK1-3 increasedby 20% and 24%, respectively, compared with those usingIPTG in the fed-batch culture. The lactose seemed to behydrolyzed by intracellular and extracellular b-galactosidaseliberated by cell lysis at the same time. Residual concentrationof glucose was maintained to a limit of detection by highperformance liquid chromatography, and galactose was notconsumed by the host strain Escherichia coli BL21(DE3).

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