Modulating the pH-activity profile of the glucose isomerase from Thermotoga marimita by introducing positively and negatively charged residues

Biophys Chem. 2024 Dec 22:318:107382. doi: 10.1016/j.bpc.2024.107382. Online ahead of print.

Abstract

Glucose isomerase is generally used in the industrial production of high-fructose corn syrup, and a heat- and acid-resistant glucose isomerase is preferred. However, most glucose isomerases exhibit low activity or inactivation at low pH. In this study, we demonstrated that two combination mutants formed by introducing positive and negative charges near the active site and on the surface of the enzyme demonstrated a successful reduction in the optimal pH and increase in the specific activity of glucose isomerase from Thermotoga maritima (TMGI). Thirteen residues, eight surface amino acids and five near the vicinity of active sites, were selected by introducing positively charged residues near the active site (mutant E237R/N298K/N337R) and negatively charged residues at the enzyme surface (mutant R112E/K220E) and were site-mutated on the basis of computational analysis. In mutants E237R/N298K/N337R and R112E/K220E, there was a decrease in the optimal pH of the glucose isomerase from 7.0 to 6.0 and 5.5, respectively, and an increase in the optimal temperature of E237R/N298K/N337R from 95 °C to 100 °C. At pH 5.5 and pH 6.0, the specific activities of R112E/K220E and E237R/N298K/N337R were 2.81 and 1.79 times greater than that of the wild-type enzyme, respectively, and their thermostabilities were greater than that of TMGI. Therefore, these two mutants (E237R/N298K/N337R and R112E/K220E) have great potential for use in the industrial production of high-fructose corn syrup. Moreover, glucose isomerase was expressed in Pichia pastoris, which demonstrated that the high expression and secretion capacity of Pichia pastoris could be used to reduce the production cost of high-fructose corn syrup.

Keywords: Active site; Glucose isomerases; High-fructose corn syrup; Protein engineering; Surface charge; pH optimum.