A superstructure-based approach was proposed for optimization of biorefineries that use Saccharina japonica as feedstock. The goal of this study was to determine the optimal flowsheet design to maximize the net present value by considering the mass and energy balance, capital and manufacturing costs. Multiple design alternatives reported in the literature were considered at each biorefinery processing stage, which transformed the superstructure optimization into a mixed integer nonlinear programming (MINLP) problem. In order to efficiently compute a solution for the resulting MINLP problem, the separable programming technique is employed by approximating the initial MINLP problem into a mixed integer linear programming (MILP) problem. The results indicated that the minimum ethanol selling price for optimal design is $1.97/gal, whereas the net present value of $61.5 million is obtained based on the current wholesale prices for both products and raw materials. Sensitivity analysis was performed to identify potential for economic improvement. The developed framework has the capacity to efficiently scan through processing alternatives to identify an economically optimal design for different potential objective functions. (C) 2018 Elsevier Ltd. All rights reserved.