Harnessing prokaryotic amino acid transporters for metabolic engineering: mechanisms and biotechnological applications

As fundamental bioactive molecules and building blocks of cellular structures, amino acids play a crucial role in sustaining life, reflected in a global market valued at tens of billions of dollars. Recently, microbial fermentation has become a leading alternative to chemical synthesis and enzymatic catalysis for amino acid production, driving the need for robust strains. Efficient transport of amino acids out of the cell is essential for strain development, as it mitigates intracellular accumulation, cytotoxicity, and feedback inhibition, thereby improving fermentation efficiency. This review summarizes the physiological characteristics of amino acid transporters and their applications in the metabolic engineering of high-performance microbial strains. In particular, it provides a comprehensive overview of how amino acid transport systems are applied to develop amino acid-producing strains by enhancing substrate uptake, increasing precursor supply, directly promoting amino acid transportation, and reducing flux through competing metabolic pathways. Furthermore, this review explores future challenges and prospects in the field, offering theoretical guidance for engineering robust microbial platforms capable of producing not only amino acids but also high-value bioproducts.