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Article Abstract
Enhancing acid tolerance of industrial microorganisms is critical for improving fermentation efficiency and sustainability. This study presents a synthetic biology approach that employs toehold switch-based acid-tolerance modules to engineer acid-tolerant strains. This toehold switch-based approach enables the construction of modules consisting of a trigger block and a switch block, generating a synthetic module library of ~10 constructs that integrate four acid-responsive promoters and 18 acid-resistance genes. Through stepwise evaluation, we identified two best synthetic modules, RE-6 and RE-38, which enabled an industrial lysine-producing strain to maintain lysine titers and yields at pH 5.5 comparable to those observed in the parent strain at pH 6.8. Transcriptional analyses revealed that upregulation of key acid-resistance genes involved in protein quality control, reactive oxygen species scavenging and redox homeostasis contributed to the enhanced acid tolerance of the engineered strains. Our study offers a powerful toehold switch-based approach for constructing synthetic modules of interest, particularly for enhancing the robustness and productivity of industrial strains.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146417 | PMC |
| http://dx.doi.org/10.1111/1751-7915.70175 | DOI Listing |
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