BACKGROUND AND OBJECTIVES: With remarkable advances in biotechnology and the advent of technologies such as CRISPR-Cas9 and precise point-mutation methods, an ideal platform has emerged to enhance the performance of Corynebacterium glutamicum in diverse biological applications. These genome modifications targeting secretion systems,promoters, and regulatory elements have significantly improved host functionality. As C.glutamicum is a powerful industrial and pharmaceutical chassis for recombinant protein production, its rational engineering is particularly critical.This study examines genetic engineering strategies to expand host capacity and boost its efficiency in modern bioprocessing. MATERIALS AND METHODS: In this structured review, studies published from 1995 to 2024 were rigorously examined. The analysis focused on the genome editing systems of Corynebacterium glutamicum, strong native and inducible promoters, synthetic promoter libraries, and shuttle vectors such as pPBEx2. RESULTS AND DISCUSSION: Efficient promoters were identified and engineered through combined experimental and bioinformatic approaches, optimizing native (PporB), inducible (PlacUV5), and synthetic (Ptrc) promoters to achieve precise expression control. Secretion pathways Sec and Tat were enhanced by overexpressing tatA and tatC and employing engineered signal peptides such as TorA and PorB, resulting in markedly increased protein export. Deletion of the CGP3 prophage and other mobile genetic elements bolstered genomic stability. Concurrent modulation of metabolic pathways and upregulation of stress-response genes (e.g.,DnaK), together with the use of optimized shuttle vectors (pEKEx2 and pVWEx1), not only raised production yields but also enabled tighter regulation of recombinant gene expression. Finally, cell-wall engineering improved permeability, facilitating more efficient release of complex proteins and transforming C.glutamicum into a robust host for biomanufacturing.
