Butanol production from corn stover via (acetone-butanol-ethanol) ABE fermentation under vacuum was studied in this work. The reactor operating strategies considered were batch, fed-batch and continuous. The integrated reactor and vacuum separation process includes energy integration by a heat-pump system as well. A mathematical model describing the dynamics of the integrated reactors and the network of compressors and heat exchangers has been developed. The dynamic process models were used to select the optimum production strategy using economic optimisation where a methodology to determine the effect of scheduling of parallel reactor operation on the sizing of the heat-pump system was developed. The results suggest that the optimal operating mode for the integrated reaction system was fed-batch. Although the fed-batch process had the highest economic potential (37.8 MM USD), the compressor work for batch process operation (36.6 MM USD) was the lowest (1.8 MJ/kg ABE, 18% lower than that of fedbatch). Continuous process operation demonstrated the lowest economic potential (23.8 MM USD) and the highest compression work (2.87 MJ/kg ABE). The energy requirements of the purification system, a double-effect distillation process, were found to be between 3.45 and 4.14 MJ/kg ABE. (C) 2018 Elsevier Ltd. All rights reserved.