Base Editors for Engineering Industrial Microorganisms: Types, Applications, and Future Perspectives

Base editing encompasses technologies that enable the direct conversion of one nucleotide base into another, typically by employing deaminases fused to programmable DNA- or RNA-binding scaffolds such as CRISPR-dCas9/nCas9. Deaminase-free editing strategies are also emerging as promising alternatives. Unlike conventional CRISPR-Cas9 systems that rely on DNA double-strand breaks (DSBs) and subsequent homology-directed repair or non-homologous end joining (NHEJ), base editors operate independently of these pathways, thus enabling continuous in vivo genome evolution and phenotypic diversification. While previous reviews have summarized base editing in plants and animals, the present review focuses specifically on base editors tailored for industrial microorganisms. We provide a comprehensive overview of deaminase-dependent and glycosylase-dependent base editors, emphasizing their applications in sculpting microbial genomes, redirecting metabolic flux, and enhancing stress tolerance. In addition, we summarize recent advances in in situ bacterial base editing, an emerging frontier for industrial strain improvement. Finally, we dissect the current limitations of these tools and propose actionable strategies to enhance editing performance and broaden their applicability. By integrating these perspectives, this review aims to guide future development and deployment of base editing technologies in both model and non-model industrial microorganisms, ultimately advancing their roles in biomanufacturing, biomonitoring, and beyond.