Glutamate decarboxylase (GAD, EC 4.1.1.15) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes the irreversible α-decarboxylation of L-glutamate to produce γ-Aminobutyric acid (GABA). As the rate-limiting enzyme in GABA biosynthesis, GAD is central to research in neuroscience, plant stress physiology, and industrial biotechnology. This review systematically summarizes the structural characteristics, catalytic mechanisms, enzymatic properties, factors affecting the activity, and activity determination methods of GAD in microorganisms, plants, and mammals. Furthermore, from the perspectives of enzyme resource mining and protein engineering, this review presents an evaluation of strategies for enhancing GAD catalytic performance and stability, including site-directed mutagenesis, directed evolution, and semi-rational design. Finally, the applications of engineered GAD in GABA biosynthesis are comprehensively analyzed.
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Funding
Key Laboratory of Industrial Biotechnology (Ministry of Education)(KLIB-KF202402)
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