Deng Jie, Gao Hua, Gao Zhen, Zhao Huaxian, Yang Ying, Wu Qiaofen, Wu Bo, Jiang Chengjian
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning, Guangxi, China.
College of Ocean and Biotechnology, Guangxi University for Nationalities, Nanning, Guangxi, China.
PLoS One. 2017 Sep 20;12(9):e0185060. doi: 10.1371/journal.pone.0185060. eCollection 2017.
L-lysine decarboxylase (LDC, EC 4.1.1.18) is a key enzyme in the decarboxylation of L-lysine to 1,5-pentanediamine and efficiently contributes significance to biosynthetic capability. Metagenomic technology is a shortcut approach used to obtain new genes from uncultured microorganisms. In this study, a subtropical soil metagenomic library was constructed, and a putative LDC gene named ldc1E was isolated by function-based screening strategy through the indication of pH change by L-lysine decarboxylation. Amino acid sequence comparison and homology modeling indicated the close relation between Ldc1E and other putative LDCs. Multiple sequence alignment analysis revealed that Ldc1E contained a highly conserved motif Ser-X-His-Lys (Pxl), and molecular docking results showed that this motif was located in the active site and could combine with the cofactor pyridoxal 5'-phosphate. The ldc1E gene was subcloned into the pET-30a(+) vector and highly expressed in Escherichia coli BL21 (DE3) pLysS. The recombinant protein was purified to homogeneity. The maximum activity of Ldc1E occurred at pH 6.5 and 40°C using L-lysine monohydrochloride as the substrate. Recombinant Ldc1E had apparent Km, kcat, and kcat/Km values of 1.08±0.16 mM, 5.09±0.63 s-1, and 4.73×103 s-1 M-1, respectively. The specific activity of Ldc1E was 1.53±0.06 U mg-1 protein. Identifying a metagenome-derived LDC gene provided a rational reference for further gene modifications in industrial applications.
L-赖氨酸脱羧酶(LDC,EC 4.1.1.18)是L-赖氨酸脱羧生成1,5-戊二胺过程中的关键酶,对生物合成能力有重要贡献。宏基因组技术是一种从未培养微生物中获取新基因的捷径方法。在本研究中,构建了一个亚热带土壤宏基因组文库,并通过基于功能的筛选策略,利用L-赖氨酸脱羧引起的pH变化指示,分离出一个假定的LDC基因ldc1E。氨基酸序列比较和同源建模表明Ldc1E与其他假定的LDCs关系密切。多序列比对分析显示Ldc1E含有一个高度保守的基序Ser-X-His-Lys(Pxl),分子对接结果表明该基序位于活性位点,可与辅因子磷酸吡哆醛结合。将ldc1E基因亚克隆到pET-30a(+)载体中,并在大肠杆菌BL21(DE3)pLysS中高效表达。重组蛋白被纯化至均一性。以L-赖氨酸盐酸盐为底物时,Ldc1E的最大活性出现在pH 6.5和40°C。重组Ldc1E的表观Km、kcat和kcat/Km值分别为1.08±0.16 mM、5.09±0.63 s-1和4.73×103 s-1 M-1。Ldc1E的比活性为1.53±0.06 U mg-1蛋白。鉴定一个宏基因组来源的LDC基因可为工业应用中的进一步基因改造提供合理参考。