Study on production enhancement of validamycin A using online capacitance measurement coupled with ^sup 1^H NMR spectroscopy analysis in a plant-scale bioreactor

Herein, an improved production of validamycin A was obtained upon developing a fed-batch strategy in a plant-scale bioreactor. The shiftin metabolic flux during validamycin A fermentation process was elucidated using the online capacitance measurement coupled with 1H NMR spectroscopy. We found that the online capacitance measurement could replace DCW for biomass detection in raw material medium during fermentation. On the basis of cell mass and residual sugar concentration, a fed-batch fermentation strategy was developed, with two times addition of 12 g/L glucose in the broth at the 49.5th and 64.5th h. Subsequently, the validamycin A concentration reached 26.0 g/L in a 60-T fermenter. The intracellular concentration of trehalose, maltose, and tryptophan had notably increased, and their accumulation had a strong relationship with validamycin A production. In this study, a metabolomics analysis method without 13C labeling, which can be applied to plant-scale fermentation in turbid broth, is being presented for the first time. In brief, the undertaken study provides a new approach for the process improvement of validamycin A production.