(531c) Industrial Platform Design for Large Scale Production of Probiotic Yeast

Probiotics are live microorganisms or microbial mixture administrated to improve human microbial balance, particularly the environment of the gastrointestinal tract and the vagina. For many years, different bacterial strains belong to Lactobacillus sp., Lactococcus sp. Streptococcus sp. and Bifidobacterium sp. are widely used as efficient probiotic strains. In addition, yeast strain such as Saccharomyces boulardii, a non-pathogenic yeast that grows optimally at body temperature, has been applied as an efficient probiotic strain in the prevention of microbial associated diarrhea. In spite of many literatures published concerning the importance of S. boulardii as probiotic strain, little information is available concerning the cell mass production of this type of yeast. The production of this strain in industrial level faces two main challenges. First, the significant low biomass production when cells cultivated in large scale due to oxygen limitation and alcohol production. Second, high sensitivity of cells to elevated temperature and dryness, and thus, the down-stream process to obtain cells in dry form requires freeze-drying step instead of the cheap spray drying. To overcome the first bottle-neck of this process, cells were cultivated in an optimized semi-defined industrial medium using exponential fed-batch cultivation strategy in 16-L stirred tank bioreactor to achieve high cell density more than 100 g/L with minimal alcohol production. This process was scaled up to 70-L and 300-L bioreactors to investigate the scalability and to complete the industrialization cycle of this process. On the other hand, to reduce the down-stream cost cells were initially adapted to dryness and to short time exposure to high temperature. Thus, spray drying was applied in downstream process instead of the conventional drying method of this yeast using the expensive freeze drying technique. In the present work, the complete new industrial platform design for large scale production of yeast probiotics will be presented.