Microbiology and Metabolic Engineering Key Laboratory of Sichuan Province, College of Life Sciences, Sichuan University, Chengdu 610064, Sichuan, People's Republic of China.
Curr Microbiol. 2010 Oct;61(4):267-73. doi: 10.1007/s00284-010-9606-5. Epub 2010 Mar 6.
In order to improve the thermostability of Escherichia coli AppA phytase, Error-prone PCR was used to randomize mutagenesis appA gene, and a gene mutation library was constructed. A mutant I408L was selected from the library by the method of high-throughput screening with 4-methyl-umbelliferylphosphate (4-MUP). The appA gene of the mutant was cloned and expressed in E. coli Origami (DE3). The recombinant protein was purified by Ni-affinity chromatography, and the enzymatic features were analyzed. The results indicated that AppA phytase activities of mutant I408L and wild-type (WT) strain remained at 51.3 and 28%, respectively, after treatment at 85°C for 5 min. It means that the thermostability enhancement of AppA phytase I408L was 23.3% more as compared with WT. The K (m) of both phytase were 0.18 and 0.25 mM, respectively, which indicated that the catalyzing efficiency of I408L was improved. AppA phytase of mutant I408L showed a significant enhancement against trypsin, which was nearly three times compared with WT. In addition, AppA phytase of mutant could be activated by Mg(2+) and Mn(2+); in contrast, it could be inhibited by Ca(2+), Co(2+), Cu(2+), and K(+) in varying degrees, and the enzymatic activity was almost lost the presence of Fe(3+) and Zn(2+). It appears that screening thermotolerant phytase of E. coli by high throughput screening with a fluorescence substrate is a fast, simple, and effective method. The mutant I408L obtained in this study could be used for the large-scale commercial production of phytase.
为提高大肠杆菌 AppA 植酸酶的耐热性,采用易错 PCR 技术对 appA 基因进行随机突变,构建基因文库。采用 4-甲基伞形酮磷酸酯(4-MUP)高通量筛选方法从文库中筛选得到一个突变体 I408L。克隆并在大肠杆菌 Origami(DE3)中表达突变体的 appA 基因。通过 Ni-亲和层析纯化重组蛋白,并分析其酶学特性。结果表明,突变体 I408L 和野生型(WT)菌株的 AppA 植酸酶活性在 85°C 处理 5 min 后分别保持在 51.3%和 28%。这意味着与 WT 相比,I408L 植酸酶的耐热性提高了 23.3%。两种植酸酶的 K(m)分别为 0.18 和 0.25 mM,表明 I408L 的催化效率提高。突变体 I408L 的植酸酶对胰蛋白酶的抑制作用显著增强,与 WT 相比几乎提高了三倍。此外,突变体的 AppA 植酸酶可以被 Mg(2+)和 Mn(2+)激活;相反,它可以被 Ca(2+)、Co(2+)、Cu(2+)和 K(+)不同程度地抑制,并且在存在 Fe(3+)和 Zn(2+)的情况下,酶活性几乎丧失。通过荧光底物高通量筛选筛选大肠杆菌耐热植酸酶是一种快速、简单、有效的方法。本研究获得的突变体 I408L 可用于植酸酶的大规模商业化生产。