Thermally triggered reversible phase transition of elastin-like polypeptide (ELP) allows for a simple, economical and scalable procedure of protein purification. This technique is especially useful for purifying salt-requiring enzymes such as halophilic enzymes which require high salt concentration to keep natural structure and activity. In this study, a highly hydrophilic/acidic beta-galactosidase cloned from halotolerant Planococcus sp.L4 was used as a target protein to apply ELP tags for purification. A high-level expression of beta-galactosidase tagged with 80 repeats of Val-Pro-Gly-Val-Gly pentapeptide (galactosidase-ELP[V-5-80]) was achieved in Escherichia coli BLR(DE3) at 21 degrees C for 24 h. accounting for around 50% of the total protein. The enzyme activity of the fusion by optimized protocol should be reached as much as 3 folds of that by rapid IPTG-induction, implying that measures to avoid possible errors during protein expression can be helpful for keeping bioactivities. The optimal condition for precipitating ELP-tagged protein was performed with a simple, rapid and sensitive method by examining the activity of supernatant after the first-round hot spin. The fusion protein aggregated effectively at 37 degrees C with 1.5 M ammonium sulfate and yielded highly pure protein with a recovery higher than 90% by one cycle. These results suggested that inverse transition cycling (ITC) process provides a potential for the large-scale purification of halophilic beta-galactosidase. (c) 2012 Elsevier Ltd. All rights reserved.