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Shake Flask to Fermentor: What Have We Learned?

Initially the concern on scale‐up of fermentation processes was with oxygen transfer. Strain stability on scale‐up was thought to be sufficiently established by serial transfer in shake flasks where conditions were homogeneous. Unfortunately, we now know that there are often mixing problems in large‐scale fermentors. The conditions within the vessel can be highly non‐homogeneous even on a macro‐scale. These non‐homogeneous variations include temperature, dissolved oxygen, and fluid shear. Such variations can cause strain degredation and failure of a strain to perform satisfactorily over long fermentation times in large‐scale vessels. Also, the highly mutated industrial strains often have hidden auxotrophy that only may be exposed in non‐homogeneous conditions. For this reason scale‐up is still an art not an exact science. We need to learn how to achieve better mixing in large‐scale fermentors.