Manufacturing butanol, ethanol, and acetone by fermenting grains has been gaining increasing interest. The conversion of grains by fermentation has been significantly enhanced through genetic engineering of enzymes. Nevertheless, the conversion attainable at present still remains very low, thereby rendering the products exceptionally dilute in the aqueous effluent streams. Hence, the downstream processing to isolate and purify the products from the fermentors is exceedingly expensive. Developing cost-effective flowsheets for the downstream processing is, therefore, crucial for enhancing the economic viability, or sustainability, of any process for biochemically manufacturing butanol, ethanol, and acetone. Various separation methods proposed in the last two decades can possibly be adopted for the downstream processing in biochemically manufacturing butanol, ethanol, and acetone. Such methods include gas stripping, distillation, extraction, adsorption, and pervaporation. The practicability of adopting any of these separation methods can be assessed variously. One rational way would be to assess it in the context of the flowsheet in which the separation method of interest is incorporated. In the current work, all plausible processing equipment and unit operations, i.e., operating units, implementing these separation methods, are selected for possible inclusion in the process at the outset. Then, the exactly defined superstructure with minimal complexity, termed maximal structure, is constructed from these operating units with the rigorous and highly efficient graph-theoretic method for process synthesis based on process graphs (Pgraphs). Subsequently, the optimal and near-optimal flowsheets in terms of cost are identified among all the feasible flowsheets recovered from all maximal structure. Finally, evaluation is made of the contribution of the cost of each operating unit implementing an individual separation method to the total cost of any of these flowsheets and the sensitivity of the latter to the variation of the former. Naturally, the cost of energy can be taken into account in addition to the equipment cost.