Yang Hongyu, Zhu Qiang, Zhou Nandi, Tian Yaping
The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.
World J Microbiol Biotechnol. 2016 Nov;32(11):176. doi: 10.1007/s11274-016-2135-z. Epub 2016 Sep 15.
Prolyl aminopeptidases are specific exopeptidases that catalyze the hydrolysis of the N-terminus proline residue of peptides and proteins. In the present study, the prolyl aminopeptidase gene (pap) from Aspergillus oryzae JN-412 was optimized through the codon usage of Pichia pastoris. Both the native and optimized pap genes were inserted into the expression vector pPIC9 K and were successfully expressed in P. pastoris. Additionally, the activity of the intracellular enzyme expressed by the recombinant optimized pap gene reached 61.26 U mL(-1), an activity that is 2.1-fold higher than that of the native gene. The recombinant enzyme was purified by one-step elution through Ni-affinity chromatography. The optimal temperature and pH of the purified PAP were 60 °C and 7.5, respectively. Additionally, the recombinant PAP was recovered at a yield greater than 65 % at an extremely broad range of pH values from 6 to 10 after treatment at 50 °C for 6 h. The molecular weight of the recombinant PAP decreased from 50 kDa to 48 kDa after treatment with a deglycosylation enzyme, indicating that the recombinant PAP was completely glycosylated. The glycosylated PAP exhibited high thermo-stability. Half of the activity remained after incubation at 50 °C for 50 h, whereas the remaining activity of PAP expressed in E. coli was only 10 % after incubation at 50 °C for 1 h. PAP could be activated by the appropriate salt concentration and exhibited salt tolerance against NaCl at a concentration up to 5 mol L(-1).
脯氨酰氨肽酶是一类特异性外肽酶,可催化肽和蛋白质N端脯氨酸残基的水解。在本研究中,通过毕赤酵母的密码子使用对米曲霉JN - 412的脯氨酰氨肽酶基因(pap)进行了优化。将天然和优化后的pap基因均插入表达载体pPIC9K,并在毕赤酵母中成功表达。此外,重组优化pap基因表达的细胞内酶活性达到61.26 U mL(-1),比天然基因的活性高2.1倍。重组酶通过镍亲和层析一步洗脱进行纯化。纯化后的PAP的最适温度和pH分别为60℃和7.5。此外,重组PAP在50℃处理6 h后,在6至10的极宽pH值范围内回收率大于65%。用去糖基化酶处理后,重组PAP的分子量从50 kDa降至48 kDa,表明重组PAP完全糖基化。糖基化的PAP表现出高热稳定性。在50℃孵育50 h后仍保留一半活性,而在大肠杆菌中表达的PAP在50℃孵育1 h后剩余活性仅为10%。PAP可被适当的盐浓度激活,并对高达5 mol L(-1)的NaCl表现出耐盐性。