Fermentation up-scaling

Although the parameters governing a whole cell-based process are numerous, the key limitation of the low productivity was clearly idenhfied as substrate and product inhibition. Substrate inhibition could conveniently be overcome by continuous feeding. A pilot-scale fed-batch experiment (551) was carried out [101] in which the feeding rate was adjusted to maintain the ketone concentrahon below 0.7 g/1. A final concentration of about 4g/l of lactones was reached within 4h. After downstream product recovery on charcoal, over 200 g of combined lactones was obtained, corresponding to a 76% yield. 

To improve productivity further, limitahon by product inhibition has also to be circumvented, but that implies a deeper modificahon of the process. A classical method is the use of a two-liquid phase process. Only small-scale experiments were carried out with moderate success [100,102,103]. Moreover, given the strong oxygen requirements of the biotransformation (cf below), the up-scaling of this method would probably be hampered. 

Hashed roan (recycling) kaded resin (uncwnpWocwwefsioo) 

The resin-based SFPR concept is appearing more and more as a general tool for highly regio-, stereo-, or enantioselective Baeyer-Villiger biotransformations. Its scope has been successfully extended to various ketones [98] or sulfides [109] and different expression systems. Thus, typically 11 of CPMO-overexpressing 

coli DH5a cells in the presence of Lewatit VPOC1163 transformed 5-15 g of 

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