Multi-parameter optimization of recombinant protein secretion in Bacillus subtilis: a review
Year: 2026
Type: article
Abstract: Bacillus subtilis is widely recognized as one of the most robust and versatile hosts for recombinant protein production. This review provides a comprehensive overview of the protein secretion pathway in B. subtilis , detailing its mechanistic basis and key limiting steps. We discuss the structural features of signal peptides (SPs) that govern efficient translocation and highlight recent advances in de novo promoter and signal peptide engineering. A particular focus is placed on the integration of artificial intelligence (AI) to predict and design optimal genetic elements. Drawing on findings from combinatorial and multi-parameter studies, we propose that future engineering strategies should move beyond maximizing individual parameters. Instead, achieving a dynamic balance across transcriptional, translational and secretion layers is essential to sustain high productivity while minimizing cellular secretion stress. This review offers a roadmap for systems-level engineering of B. subtilis as a next-generation protein production platform.
Source: Microbial Cell Factories
Institutions: Academy of Sciences Republic of Uzbekistan, Institute of Microbiology Academy of Sciences of the Republic of Uzbekistan, Heinrich Heine University Düsseldorf, Chinese Academy of Sciences, Institute of Microbiology, University of Chinese Academy of Sciences, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Beijing University of Chemical Technology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,590
OpenAlex ID: W7222811144
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