Liu Xiaofeng, Zhang Qian, Zhou Nandi, Tian Yaping
The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.
Mol Biotechnol. 2017 Mar;59(2-3):84-97. doi: 10.1007/s12033-017-9994-x.
Urea in alcoholic beverage is a precursor of ethyl carbamate (EC), which is carcinogenic. Enzymatic elimination of urea has attracted much research interest. Acid urease with good tolerance toward ethanol and acid is ideal enzyme for such applications. In the present work, the structural genes of urease from Providencia rettgeri JN-B815, ureABC were efficiently expressed in E. coli BL21(DE3) in an active form (apourease) exhibiting both urease and urethanase (hydrolyze EC) activities. The specific activities of the purified apourease were comparatively low, which were 2.1 U/mg for urease and 0.6 U/mg for urethanase, respectively. However, apourease exhibited good resistance toward ethanol and acidic conditions. The relative activities of urease and urethanase remained over 80% in the buffers within pH 4-7. And the recoveries of both urease and urethanase activities were more than 50% in 5-25% ethanol solution. Apourease was utilized to eliminate urea in wine, and the residual urea in model wine was less than 50% after treatment with apourease for 30 h. Then 3D structure of UreC was predicted, and it was docked with urea and EC, respectively. The docking result revealed that three hydrogen bonds were formed between urea and amino acid residues in the active site of urease, whereas only one hydrogen bond can be formed between EC and the active center. Moreover, EC exhibited greater steric hindrance than urea when combined with the active site. Due to the low specific activities of apourease, both structural genes and accessory genes of urease were co-expressed in E. coli BL21(DE3). The holoenzyme was expressed as inclusion body. After renaturation and purification, the specific activities of urease and urethanase reached 10.7 and 3.8 U/mg, which were 5.62-fold and 6.33-fold of those of apourease, respectively. Therefore, accessory subunits of urease play an important role in enhancing urease and urethanase activities.
酒精饮料中的尿素是致癌物质氨基甲酸乙酯(EC)的前体。酶法去除尿素引起了众多研究兴趣。对乙醇和酸具有良好耐受性的酸性脲酶是此类应用的理想酶。在本研究中,雷氏普罗威登斯菌JN - B815的脲酶结构基因ureABC在大肠杆菌BL21(DE3)中以活性形式(脱辅基脲酶)高效表达,该脱辅基脲酶同时具有脲酶和脲基甲酸酯酶(水解EC)活性。纯化后的脱辅基脲酶的比活性相对较低,脲酶和脲基甲酸酯酶的比活性分别为2.1 U/mg和0.6 U/mg。然而,脱辅基脲酶对乙醇和酸性条件表现出良好的耐受性。在pH 4 - 7的缓冲液中,脲酶和脲基甲酸酯酶的相对活性保持在80%以上。在5 - 25%的乙醇溶液中,脲酶和脲基甲酸酯酶的活性回收率均超过50%。脱辅基脲酶被用于去除葡萄酒中的尿素,用脱辅基脲酶处理30小时后,模拟葡萄酒中的残留尿素低于50%。然后预测了UreC的三维结构,并分别将其与尿素和EC进行对接。对接结果显示,尿素与脲酶活性位点的氨基酸残基之间形成了三个氢键,而EC与活性中心之间只能形成一个氢键。此外,EC与活性位点结合时比尿素表现出更大的空间位阻。由于脱辅基脲酶的比活性较低,脲酶的结构基因和辅助基因在大肠杆菌BL21(DE3)中共同表达。全酶以包涵体形式表达。复性和纯化后,脲酶和脲基甲酸酯酶的比活性分别达到10.7和3.8 U/mg,分别是脱辅基脲酶的5.62倍和6.33倍。因此,脲酶的辅助亚基在提高脲酶和脲基甲酸酯酶活性方面发挥着重要作用。