The alternative fuel butanol can be produced via acetone-butanol-ethanol (ABE) fermentation from renewable resources, i.e. biomass. Expensive feedstocks and the high costs for the separation of ABE from the dilute fermentation broth in the downstream processing have so far prohibited the industrial-scale production of bio-butanol. The low productivities and butanol yields of ABE batch fermentation can be increased by continuous fermentation with cell recycle and integrated product removal. In order to facilitate an effective and energy-efficient product removal, we suggest to apply a hybrid extraction-distillation process with ABE extraction in an external column. The removal of ABE outside the fermenter in an extraction column is favored from an operational point of view. By means of computer-aided molecular design (CAMD), mesitylene has been identified as a new solvent for ABE extraction from the fermentation broth. The solvent properties of mesitylene are compared to those of oleyl alcohol, which is the most common solvent for ABE extraction. Subsequently, we propose a hybrid extraction-distillation downstream process for product removal and purification. It is shown that the specific energy demand of this process is significantly lower when mesitylene is used as extraction solvent instead of oleyl alcohol.