Rapid strain evaluation using dynamic DO-stat fed-batch fermentation under scale-down conditions.

While large amount of strains can be quickly generated via metabolic engineering, the speed/efficiency of evaluating each strain becomes the bottleneck in the process from strain development to final production. In this chapter, a method is introduced to rapidly evaluate strain performance in fed-batch fermentation mode by using dynamic dissolved oxygen stat feed back control with no additional advanced online measurement. In addition, a scale-down feature is integrated in the method to mimic the limitation of oxygen transfer in large-scale vessels, so that strains can be evaluated under the conditions close to that in large-scale bioreactors. The method has been implemented in several commercial standard benchtop scale fermentation systems with different fermentation control software.