Date of Award

8-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

Nina Goodey

Committee Member

Jim Dyer

Committee Member

Jaclyn Catalano

Abstract

Thermotoga maritima indole-3-glycerol phosphate synthase (T. maritima IGP synthase) is a monomeric thermostable enzyme. T. maritima IGP synthase catalyzes the fifth step in the tryptophan biosynthesis pathway, which functions in the conversion of 1-(o-carboxyphenylamino)-1-deoxyribulose-5-phosphate (CdRP) to indole-3-glycerol phosphate (IGP). This research investigates the temperature-dependent catalytic activity and substrate binding of the thermophilic enzyme T. maritima IGP synthase to understand its unique adaptations to environments such as hot springs. Enzyme kinetic assays, kinetic solvent viscosity effects (KSVE), and Arrhenius plots were used to analyze the catalytic activity and substrate binding of wildtype and E47D T. maritima IGP synthase at temperatures ranging from 25 °C to 80 °C. We propose that the kinetic parameters governing these processes have different temperature dependencies. Previous studies reported the wildtype kcat value of 0.11 s-1 and a KM value of 0.006 μM at 25 °C. Here we report that the wildtype has a kcat value of 0.15 s-1 ± 0.01 and a KM value of 0.033 ± 0.007 μM, which suggests a 6-fold decrease in substrate binding affinity. The E47D resulted in a lower kcat value of 0.018 s-1 ± 0.001 and a decreased KM value of 0.008 ± 0.003 μM at 25 °C, indicating higher substrate affinity. However, temperature effect revealed high catalytic activity at higher temperatures. These results demonstrate that the E47D mutation in the active site residues of IGP synthase drastically reduces its catalytic activity but contributes significantly to its thermostability. These findings highlight the significance of residue E47 in T. maritima IGP synthase.

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