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Transcriptional regulator-based biosensors for biomanufacturing in Corynebacterium glutamicum





1. Introduction
Intracellular biosensors based on transcriptional regulators have emerged as critical tools in the realm of biomanufacturing, especially for monitoring intracellular metabolites and aiding in strain optimization. Corynebacterium glutamicum, as a robust industrial microorganism, offers an excellent platform for deploying these biosensors, thereby enhancing the precision of biochemical production processes. This review focuses on the key roles, design principles, and improvements related to transcriptional regulator-based biosensors in C. glutamicum, paving the way for future advancements in microbial engineering.

2. Types and Mechanisms of Transcriptional Regulators in C. glutamicum
Transcriptional regulators, including repressors and activators, serve as the core sensing elements of intracellular biosensors. In C. glutamicum, regulators like LysG, Lrp, and AmtR recognize specific metabolites and trigger responsive genetic circuits. Understanding the interaction between these regulators and their corresponding ligands provides a molecular basis for designing effective biosensors that are both specific and sensitive.

3. Principles of Biosensor Design Based on Transcriptional Regulators
Effective biosensor construction hinges on key principles such as selecting highly specific transcriptional regulators, optimizing promoter-regulator combinations, and tuning reporter gene expression. Rational circuit design and modularity are crucial to maximize the biosensor's responsiveness and minimize noise, ensuring accurate and reliable semi-quantitative intracellular assessments.

4. Applications of Transcriptional Regulator-Based Biosensors in C. glutamicum
These biosensors have revolutionized high-throughput screening processes for production strain improvement, enzyme evolution, and metabolic flux analysis. Applications include enhancing amino acid production (like lysine and glutamate), optimizing pathways for novel chemical synthesis, and enabling dynamic pathway regulation based on real-time metabolite levels.

5. Strategies for Improving Biosensor Performance
Several measures have been developed to enhance biosensor efficacy, including directed evolution of regulators, promoter engineering, increasing dynamic range, improving signal-to-noise ratios, and utilizing synthetic biology tools for fine-tuning regulatory responses. Such strategies ensure biosensors maintain stability, specificity, and adaptability under industrial fermentation conditions.

6. Challenges and Future Perspectives
Despite the impressive progress, challenges like limited regulator availability, cross-reactivity, and metabolic burden remain. Future research will likely focus on expanding the library of transcriptional regulators, integrating AI-guided biosensor optimization, and developing multiplexed biosensing systems. These advancements will further solidify transcriptional regulator-based biosensors as indispensable tools in smart biomanufacturing and synthetic biology.


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#BiosensorTech #Biomanufacturing #MicrobialEngineering #CorynebacteriumGlutamicum #SyntheticBiology #IndustrialBiotech #MetaboliteDetection #SmartBiosensors #AminoAcidProduction #HighThroughputScreening #DirectedEvolution #MetabolicEngineering #BiotechInnovation #IntracellularSensing #BiosensorDesign #FutureBiotech #MetaboliteMonitoring #IndustrialMicrobiology #NextGenBiomanufacturing #BioProcessOptimization #PrecisionBiotech #BiotechApplications #SmartManufacturing #MicrobialBiotech #InnovationInBiotech,

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