Evaluation and directed evolution for thermostability improvement of a GH 13 thermostable α-glucosidase from Thermus thermophilus TC11

对嗜热栖热菌TC11菌株中GH 13耐热α-葡萄糖苷酶的热稳定性进行评价和定向进化以提高其热稳定性

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Abstract

BACKGROUND: Thermal stable α-glucosidases with transglycosylation activity could be applied to the industrial production of oligosaccharides as well as conjugation of sugars to biologically useful materials. Therefore, α-glucosidases isolated from thermophiles have gained attention over the past decade. In this study, the characterization of a highly thermostable α-glucosidase and its thermostability improved mutant from newly isolated strain Thermus thermophilus TC11 were investigated. RESULTS: The recombinant α-glucosidase (TtAG) from Thermus thermophilus TC11 was expressed in Escherichia coli BL21 (DE3) and purified. The purified enzyme had a molecular mass of 184 kDa and consisted of 59-kDa subunits; it showed hydrolytic activity for pNP-α-D-glucopyranoside (pNPG), sucrose, trehalose, panose, and isomaltooligosaccharides and very low activity for maltose. The highest specific activity of 288.96 U/mg was observed for pNPG at 90 °C and pH 5.0; Pb(2+) provided a 20 % activity increase. TtAG was stable at 70 °C for more than 7 h and had a half-life of 195 min at 80 °C and 130 min at 90 °C. Transglycosylation activity was also observed with sucrose and trehalose as substrates. TtAG showed differences on substrate specificity, transglycosylation, multimerization, effects of metal ions and optimal pH from other reported Thermus α-glucosidases. One single-substitution TtAG mutant Q10Y with improved thermostability was also obtained from random mutagenesis library. The site-saturation mutagenesis and structural modelling analysis indicated that Q10Y substitution stabilized TtAG structure via additional hydrogen bonding and hydrophobic interactions. CONCLUSION: Our findings indicate that TtAG is a highly thermostable and more acidic α-glucosidase distinct from other reported Thermus α-glucosidases. And this work also provides new insights into the catalytic and thermal tolerance mechanisms of α-glucosidases, which may guide molecular engineering of α-glucosidase and other thermostable enzymes for industrial application.

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