Transporter engineering using GadC for enhanced GABA secretion in yeast

A non-proteinogenic amino acid, gamma-aminobutyric acid, finds widespread application in medications and functional foods. Gamma aminobutyric acid (GABA) has been proven to improve cognitive function, reduce blood pressure, and prevent seizures. The scalability and sustainability of GABA production is challenging through traditional techniques. GABA biosynthesis through Microbial systems like Saccharomyces cerevisiae, lactic acid bacteria, and Escherichia coli are viable alternative, which are being studied for their ability to produce GABA. S. cerevisiae, classified as Generally Regarded as Safe (GRAS), is a ideal candidate due to its significant fermentation capability, adaptability, well-characterized genetics and has well optimized gene manipulation techniques for metabolic engineering. The overall production of GABA is affected due to its intracellular accumulation and metabolic load caused by yeast’s cell division limit the GABA export. Transporter engineering offers a solution by facilitating effective product export by targeting efficient export of GABA. GADC, a glutamate/GABA antiporter identified in E. coli, facilitates glutamate import and GABA export across membranes. The heterologous expression of GADC in the yeast will enhance the GABA secretion and reduce GABA toxicity inside the cell. This review highlights the strategies for the effective production of GABA and analyses the significance of transporter engineering, and its potential in metabolic engineering which allow the successful integration of GADC, an antiporter in yeast to develop efficient GABA-producing yeast for food and therapeutic applications.