| Summary: | In aerobic environments, bacteria are exposed to reactive oxygen species (ROS). To avoid an excess of ROS, microorganisms are equipped with powerful enzymatic and non-enzymatic antioxidants. <i>Corynebacterium glutamicum</i>, a widely used industrial platform organism, uses mycothiol (MSH) as major low molecular weight (LMW) thiol and non-enzymatic antioxidant. In aerobic bioreactor cultivations, <i>C. glutamicum</i> becomes exposed to oxygen concentrations surpassing the air saturation, which are supposed to constitute a challenge for the intracellular MSH redox balance. In this study, the role of MSH was investigated at different oxygen levels (pO<sub>2</sub>) in bioreactor cultivations in <i>C. glutamicum</i>. Despite the presence of other highly efficient antioxidant systems, such as catalase, the MSH deficient Δ<i>mshC</i> mutant was impaired in growth in bioreactor experiments performed at pO<sub>2</sub> values of 30%. At a pO<sub>2</sub> level of 20%, this growth defect was abolished, indicating a high susceptibility of the MSH-deficient mutant towards elevated oxygen concentrations. Bioreactor experiments with <i>C. glutamicum</i> expressing the Mrx1-roGFP2 redox biosensor revealed a strong oxidative shift in the MSH redox potential (<i>E</i><sub>MSH</sub>) at pO<sub>2</sub> values above 20%. This indicates that the LMW thiol MSH is an essential antioxidant to maintain the robustness and industrial performance of <i>C. glutamicum</i> during aerobic fermentation processes.
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