In this work, the Plantwide Control (PWC) problem of a continuous bio-ethanol process is investigated from a Plantwide Optimizing Control (PWOC) perspective. PWOC addresses the plantwide control problem integrating real-time optimization and control for optimal operation. Two different PWOC approaches have been considered: A Single-Layer Direct Optimizing Control approach (one-layer) and a Multi-Layer without Coordination approach (two-layer). The performance of these two PWOC approaches is compared with more traditional Decentralized architectures, demonstrating the benefits of using Plantwide Optimization-based Control strategies in bioprocesses.