Biorefineries are novel biotechnological routes designed to generate sustainable processes from renewable raw materials. The valorization of orange peel waste (OPW) provides high-value products based on their composition. The economic optimization of biorefineries through conceptual design and generation of superstructures based on the analysis of processing units is a topic of great interest. This work aimed to obtain the most profitable biorefinery through economic optimization strategies based on high-value-added products from OPW. Two stages were considered: The first stage consisted of the conceptual design of multiple OPW processing units (production of essential oil, mucic acid, phenolic compounds, biogas, among others). An OPW flow rate of 140 kg/h was selected as the base case. From the stand-alone units, a biorefinery superstructure (second stage) was designed. Finally, the units with the best mass and energy results were selected in order to maximize the net present value (NPV) and obtain an optimal biorefinery configuration. The results evidenced that the production of essential oil and biogas presented the best yields (2.61 mL and 0.028 m3 per kg OPW, respectively). This biorefinery configuration obtained an NPV of −7.7 mUSD from the base case. Through the evaluation of the different superstructure configurations, the combined production of essential oil, biogas, and mucic acid and a scale-up of over 22 times the base case generated the minimum processing scale. Under a Colombian context, the implementation of the biorefineries analyzed are promising since the minimum processing scale contemplated only 8.8% of the OPW production. Efforts to increase yields and decrease capital and operating expenses while keeping environmental impacts low should be pursued.
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