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One-step chromatographic purification and functional characterization of Helicobacter pylori neutrophil-activating protein expressed in Bacillus subtilis
Thesis

One-step chromatographic purification and functional characterization of Helicobacter pylori neutrophil-activating protein expressed in Bacillus subtilis

林志昌
Masters, 國立清華大學, 分子與細胞生物研究所
2011

Abstract

單一步驟色層分析純化枯草桿菌表達之胃幽門螺旋桿菌嗜中性白血球激活蛋白 One-step chromatographic purification of Helicobacter pylori neutrophil-activating protein expressed in Bacillus subtilis
Helicobacter pylori (H. pylori) is a pathogen that causes the gastric mucosal diseases. H. pylori neutrophil-activating protein (HP-NAP) is a virulent factor of H. pylori and has the ability to activate various immune cells such as neutrophils. Recombinant DNA technology for expressing HP-NAP is a useful tool to study the function of HP-NAP. Bacillus subtilis (B. subtilis) is a bacterium commonly used to express recombinant proteins for avoiding contamination of endotoxin. Though B. subtilis was served as a host for the expression of recombinant HP-NAP, only one strategy for purification of recombinant HP-NAP expressed in B. subtilis has been reported. In this study, B. subtilis was served as a host for the expression of recombinant HP-NAP and DEAE ion-exchange chromatography was utilized for purification of recombinant HP-NAP. The optimized culture time for expression of HP-NAP in my B. subtilis expression system was around 12 to 15 hr. To determine the optimal purification condition for obtaining HP-NAP with high purity, DEAE Sephadex resin and DEAE Sepharose resin at pH 7.0, 7.5, and 8.0 were utilized to determine the optimal purification condition. HP-NAP was remained in the unbound fraction by DEAE Sephadex resin at pH 8.0. HP-NAP was then purified by a single DEAE Sephadex ion-exchange column. The flow-through fractions containing HP-NAP with purity exceeding 92 % was obtained. The purified HP-NAP assembled into a multimeric protein with secondary structure of α-helix and stimulated the production of reactive oxygen species from neutrophils. Thus, HP-NAP can be efficiently purified from B. subtilis expression system by collection of flow-through fraction using DEAE Sephadex resin at pH 8.0.

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