Fig. 6: Adaptive laboratory evolution improves the tolerance of C. glutamicum to viscous solution.

A Fed-batch cultivation of CGHA-123 and CGHA-125 in a 5-L fermenter. Real-time glucose consumption, cell density (OD₆₀₀), and HA yield are plotted. B Effect of HA (MW 0.8−1 MDa) dissolved in culture broth on growth and glucose uptake by the CG-HA-Resistant strain, which adaptively evolved from C. glutamicum ATCC13032 in a high concentration HA solution. C Differential COG clusters indicating transcriptional differences between CG-HAT and wild-type C. glutamicum. The vertical axis shows COG classification, while the horizontal axis shows the number of differential genes. D Diagram of CG-HAT metabolism showing gene expression changes measured by transcriptomics analysis. Red and blue arrows indicate upregulated and downregulated genes, respectively. Samples were collected at the 24 h time point (refer to B for cultivation details). E Fed-batch cultivation of C. glutamicum CGHA−125 in a 5-L fermenter. The culture was supplemented with LHyal hyaluronidase at the final concentration of 10,000 U mL⁻¹ at 16 h. Statistical evaluation (p-value) was performed by a two-sided t test. All data (excluding transcriptomics analysis) are expressed as mean ± S.D. from three (n = 3) independent biological replicates. Transcriptomics analysis data are expressed as mean ± S.D. from two (n = 2) independent biological replicates. Source data are provided as a Source Data file.