Multi-parameter optimization of recombinant protein secretion in Bacillus subtilis: a review.

Authors

Askar Kholikov, Khushnut Vokhidov, Barno Alimova, Ozodakhon Pulatova, Yulong Zhang, Shihui Yang, Guimin Zhang, Yihua Chen, Akhmadzhan Makhsumkhanov

Published in

Microbial cell factories. Volume 25. Issue 1. Oct 17, 2026. Epub Oct 17, 2026.

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.

PMID:
42907859
Bibliographic data and abstract were imported from PubMed on 23 Oct 2026.

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