The acetone-butanol-ethanol (ABE) fermentation from corn stover was considered. We propose, study and optimise, via process simulation (using MATLAB (R) and Aspen Plus (R)) the use of fermentation tanks in-series and in situ product recovery by vacuum evaporation. As the operating time of continuous fermentation processes is usually limited at less than 500 h, shutdown and start-up of the reactors are considered and optimised. A multi-objective optimisation methodology that considers economics as well as the energy requirements of the process was used. The optimal configuration was found to be five fermentation tanks-in-series where the first and the last reactors are operated at atmospheric pressure, and the intermediate vessels are operated under vacuum. The economic potential using this configuration was found to be 45% higher than that of vacuum fermenters operating in parallel (continuous operating mode). Also, the total fuel requirements for ABE recovery and purification system were as low as 7 MJ kg(-1) butanol, a reduction of between 4 and 33% when compared to a parallel configuration of batch, fed-batch or continuous fermenters. The energy efficiency of this recovery and reaction system was as high as 74% when co-generation is considered. (C) 2020 Elsevier Ltd. All rights reserved.