Stress modulation strategies in Kluyveromyces marxianus: Unravelling the effects of shear force and aeration for enhanced specific ergosterol production

Ergosterol, as a precursor for synthesising useful molecules like vitamin D2, possesses significant physiological functions in both fungal and human systems. In fungi, ergosterol plays a crucial role in stress responses. In contrast to Saccharomyces cerevisiae yeast, the changes in specific ergosterol content of Kluyveromyces marxianus under various stress conditions are less known. This study investigated how ergosterol content changes in response to different stress factors. Carbon to nitrogen (C/N) ratio was examined using experimental design. The effects of aeration and shear force beside constant overall volumetric mass transfer coefficient (KLa) were examined. Cell growth and specific ergosterol content were investigated using ethanol stress during a two-stage fermentation. Based on the results, contradictory settings regarding C/N ratio and shear force were found to be favourable for cell growth and specific ergosterol content. However, increased aeration consistently elevated specific ergosterol content and favoured cell growth as well (2.5-fold and 1.5-fold, respectively). In K. marxianus fermentations, higher ergosterol yield can be achieved through a two-stage fermentation (138.9 mg L−1 compared to 52.9 mg L−1), where the first stage provides favourable conditions for cell growth, and the second stage involves stress (beneficial for ergosterol production) conditions. Conclusions drawn from the two-stage fermentation results suggest that early transitioning of cell growth to the second phase will not result higher adaption and specific ergosterol content compared to the transition at the end of exponential growth phase.